Hoffmann, Peter M. Life’s Ratchet: How Molecular Machines Extract Order from Chaos. New York, New York: Basic Books, 2012.
This book is 288 pages in length (paperback version published by Basic Books). It describes how physics, chemistry, and biology intersect to define what life is in terms of what turns seemingly inert molecules collectively into a self-propelling molecular machine driving what we know as life. At the molecular level, the author notes that the “secret of life’s activity is found at the scale of a nanometer”. Peter Hoffmann is a physicist whose conversion to biology began when, as a doctoral student, he used an atomic force microscopy to view deposits of DNA molecules. Years later, after inheriting a collaboration as a Wayne State University professor with a molecular biologist measuring the “motions of particular molecular machines implicated in the spread of cancer”, he changed course, reinforced his biology knowledge, and started a new research direction on the science of molecular machines (from the Introduction section of the book).
INTRODUCTION: WHAT IS LIFE?
In the introduction to the book, the author gives a preview of what the book aims to accomplish for the reader. The goal of this book is to answer the question to which the book title alludes to: What controls this collection of molecules into a life-giving machine? The author’s short and cryptic answer is the “force that drives life is chaos”. The author will relate the many discoveries by philosophers early in the debate and the scientists to explain “what it takes to turn a molecule into a machine and many molecular machines into a living cell”/
CHAPTER 1 – THE LIFE FORCE
This chapter traces very early ideas arising from debates about what gives life to living organisms. Starting from the creation of the universe, the author notes that “All life started as a circle dance of molecules billions of years ago.” It then goes on to give a summary of how the discourse on what constitutes life has evolved over the ages beginning from ideas put forth by Greek philosophers. For hundreds of years, the debate about what constitutes “life” has centered on the concepts of “purpose and mechanism”. The author states that the three most prominently held explanations for life, starting from the Greek philosophers to the early-19th century biologists are embodied in the philosophies of the following believe systems: animism, vitalism, and mechanism/atomism. The practice of medicine gave the first empirical insinuations in this debate that contributed to an increasingly scientific and quantitative knowledge of the workings of the human body and offered some concrete evidence related to the debate of what constitutes life. For example, William Harvey was noted as being one of the first to infuse a more quantitative method of understanding of the workings of the human body questioning how the heart could possibly be the source of blood and where it eventually by measuring blood volume and pump rates. Studies and analyses which were mainly proponents of the mechanical view helped user in the scientific revolution of which Galileo Galilei (1564 – 1642) and Isaac Newton (1642 – 1726) were the major players. Both of these men were atomists and used experiment and reason to investigate nature. This more mechanical and atomistic view emerging during the scientific revolution helped propel the pursuit of instruments (with help from improvements in the understanding of optics) to study the living world, i.e. the microscope being one of the most important. The microscope gave the first glimpse of the fundamental unit of life, the cell, unbeknownst to these scientists who first observed their presence. In his most popular work, L’homme machine, de la Mettrie concluded that organisms function as a result of their physical and mechanical make-up based on observations of how bodily and mental functions were altered by injury and the observation that muscle tissue even without being attached to a living body. Animal heat was also big on the mind of those studying the basis of life. Before Harvey’s time, Galen had correctly suggested a relationship between food and heat and respiration. Further experiments by Boyle, Mayow, and Lavoisier contributed some solid observation supporting this relationship. The birth of modern biology in the 19th century ushered in new methods and new ideas for investigating the “self-sustaining, self-organizing activity” basic attribute of life. In the field of embryology, the thinkers were divided along the lines of preformationists and the epigenesists but this era also gave birth to the teleomechanistic philosophy and ideas supporting vitalist views. The teleomechanistic views of Kant and Blumenbach led to the development of the cell theory, the idea that all living organisms are composed of fundamental units called cells. In de la Mettrie’s view, however, irritability is evidence of the purely mechanistic basis for life. The study of irritability gained traction using new methods of applying electricity to animal parts. These experiments and observations suggested that electricity could be the vital force propounded by many believers. The mid-19th century saw the revival of the mechanistic view driven by the work of Charles Darwin (1809 – 1882) who “destroyed teleology” and Hermann von Helmholtz (1821 – 1894) who “vanquished the vital force”. Helmholtz’s dismissed any utility of the vital force theory instead suggesting that energy must be conserved. His experiments showed that “all the hallmarks of being alive, from animal heat to irritability – had to occur within the energy budget prescribed by the physicochemical world”. By the end of the 19th century, the success of these mechanistic studies brought to light the fact that biology, physics, and chemistry must intersect to explain what gives life to organisms but did not answer the fundamental question issue of “purpose”. Charles Darwin and Alfred Russell Wallace provided an answer when they developed the theory of evolution based on natural selection. In his Origin of the Species published in 1859, Darwin presented his observations and his arguments for natural selection as the driving force of evolution: variations within individuals of a given species that favor reproductive success lead to progeny, thus survival and propagation. Mendel’s work on genetics and inheritance answered the follow-up question of how those traits leading to survival and propagation are transferred to the offspring: “traits are inherited whole, and that traits from each parent can be combined in various ways in the offspring”. The fact that some of these individual traits from parents can be conserved, and not always blended, was crucial to Darwin’s theory for only through the complete conservation and transfer of a specific trait that favor reproduction and not its dilution can lead to the trait’s propagation within the species. In the next chapter, the author will answer the question of what gives rise to these variations.
CHAPTER 2 – CHANCE AND NECESSITY
In the minds of many scientists and philosophers pondering what life is, randomness was not entertained at all as a viable player in the discussion until the end of the 19th century. This chapter starts off with a brief history of the development of statistics and the calculation of probabilities. The author used Pascal’s triangle as an early example of calculating the number of times one can choose a certain number of items (k items) out of n available items. This number can also be calculated using the binomial coefficient expression: n!/(n-k)!k! “Statistics has been called the theory of ignorance” but it “provides the clues to understanding the underlying regularities or the emergence of new phenomena arising from the interaction of many parts.” The real story started when biologists themselves began to apply statistics in their own studies of organisms with Galton and Quetelet being the pioneers of these extensive studies. Charles Darwin’s cousin, the mathematician Francis Galton, applied Quetelet’s ideas (“how the error law, the normal distribution, and the central limit theorem governed almost everything”) to a wide range of biological phenomena: heights, masses of organs, and circumferences of limbs and found that they all follow a normal distribution. It is these statistics that Mendel used to develop his laws of heredity. In the section “Randomness and Life: Three Views”, the author described the beliefs of the main players in the role of randomness in understanding life: the how and why of the many phenomena of life and life itself can be understood given enough understanding of the complexities involved (Thompson); life events happen due to a higher purpose reconciling science and religion (Chardin); and the beginning of life is an improbable event but once it happened, evolution and the game of chance took over (Monod). These beliefs can summarized into two dichotomies: dichotomy of mechanics (“mere physics”) versus higher forces (life forces, the soul) and the dichotomy of chance and necessity. The physicists found themselves at the intersection of mechanics (physical forces) and necessity. With the development of the kinetic theory which evolved and broadened into the Laws of Thermodynamics and mathematically sharpened into Statistical Mechanics, they finally found a way to incorporate and tame randomness into their efforts to explain (and predict) the properties of matter based on the existence of atoms: with well-defined probability distributions developed by averaging over large numbers the random motions of atoms. Quantum mechanics came into the picture in the early 19th century replacing the “iron-clad model of necessity, classical physics” with a “fundamentally statistical picture of nature”. Meanwhile, developments have been occurring in biology. Chromosomes (bundles of DNA) and their duplication during cell division were known by 1882 but it was not until 1900 that a connection was made between chromosomes and Mendel’s hereditary traits. By 1909, genetic experiments were being conducted on fruit fly drosophila by Thomas Hunt Morgan (1866 – 1945). Morgan discovered that traits are not independent as Mendel thought but are linked suggesting that “traits were contained in some kind of linear arrangement on chromosomes with nearby traits more likely to be inherited together. The mixing of traits was assigned to a crossing-over of linear molecules.” By 1920, it was clear that hereditary information was contained in the linear arrangement of the chromosomes. In 1926, Joseph Muller discovered after years of experimentation and using a controlled dose of x-ray that radiation increased the probability of new genetic traits being created due to mutations. This correlation was later refined with the help of Max Delbruck and they subsequently showed that the mutation rates depend on temperature and x-ray dose. In the words of the author, this sequence of events during the first half of the 20th century illustrates how “previously mysterious biological processes, such as heredity and variation, became connected to measurable physical (molecular) entities”. Erwin Schrodinger got a hold of these ideas and expounded on them, not correctly all the time. Based on Delbruck and others’ data, he surmised that this genetic entity must be a molecule of about a thousand atoms with very stable bonds that can withstand the elevated thermal motions with the cell. To contain a large complex amount of information, they have to be aperiodic or non-repetitive. We now know of course that the genetic material is an “aperiodic” polymer called DNA). Towards the end of the chapte, the author offers the following statement to reconcile the interplay between necessity, laws of nature, and randomness: “Life can best be understood as a game of chance – played on the chessboard of space and time with rules supplied by physics and mathematics.” These games begin at the level of the atoms
CHAPTER 3 – THE ENTROPY OF A LATE-NIGHT ROBBER
The author begins this chapter by asking the following questions of how organized living organisms can emerge from the chaos and random motions of atoms and molecules and specifically when that threshold is crossed. To answer these questions, the author suggests starting from the fundamental building blocks of matter, atoms and molecules, and looking at how these particles that are in constant motion come together to create ordered objects. In the late 1800’s, three scientists focused their research on this: Boltzmann, Maxwell, and Gibbs. The main focus of their study was how gaseous particles constantly in random motion result in macroscopic properties that follow the gas laws. To answer this, they developed statistical mechanics: “applying statistics to the chaos of atoms and molecules, they found that averaged over time and space, the randomness of atomic motion gives way to order and regularity”. Using statistical mechanics, Maxwell and Boltzmann showed that the range of particle speeds in a gas follows a normal distribution. Energy distribution is an important aspect of how the individual behavior of atoms and molecules give rise to macroscopic properties. The behavior of atoms and particles is governed by energy conservation, the strictest law of nature. The kinetic energy of atoms and molecules comes from thermal motion. It was Count Rumford who first arrived at the conclusion that heat is a form of energy after observing the kinetic energy of a metal cylinder boring a cannon was converted to heat. This interrelationship between heat and kinetic energy was the focus of studies done by Maxwell, Boltzmann, and others who developed kinetic theory which had to assume the existence of small particles such as atoms that are in constant motion. Atoms were first discovered by Robert Brown after he observed random motion of pollen grains now referred to as Brownian motion. Albert Einstein years later proved that the random motion of pollen grains was due to the random motion of much smaller particles. To bridge the behavior at this level to observable macroscopic properties is one of the goals of thermodynamics: the science that deals with thermal energy and is the macroscopic “sister science” of statistical mechanics. It is “what emerges when we average the random motions of atoms using tools of statistical mechanics.” How the thermal energy of atoms and molecules can be converted into other forms depends on the distribution of energies among the individual particles. While temperature gives a direct measure of the average kinetic energy, macroscopic properties (or macrostates) cannot tell us much about the energies and speeds of individual atoms (or microstates). To understand why some forms of energy are more usable than others, the concept of entropy is discussed in terms of microstates. A disordered arrangement where particles are randomly positioned is more probable because there are more microstates leading to this macrostate. The author makes the following comparison in terms of the entropy “content” of energy: gravitational energy is low-entropy energy while heat is high-entropy energy. Energy is dissipated in processes like friction and impact which “are great randomizers of energy.” Nature tends toward dissipation of energy into a less usable form and low-entropy energy that is “completely organized, concentrated, and tidy is a rather artificial, low-probability situation.” This is reflected in the author’s statement of the second law of thermodynamics: “There can be no process whose only result is to convert high-entropy (randomly distributed) energy into low-entropy (simply distributed or concentrated) energy. Moreover, each time we convert one type of energy into another, we always end up overall with higher-entropy energy. In energy conversions, overall entropy always increases”. Entropy is a measure of the degree to which energy is dispersed (positional entropy ultimately only contributes to the total energy entropy because the energy of a particle is dependent on position but also on other modes of motions irrespective of position). Entropy is not just disorder. An example of the above is the difference in entropy between randomly stacked particles (which have a lower entropy, narrower energy distribution) and orderly stacked marbles (higher entropy, more freedom of motion). Many biological structures that are highly ordered can spontaneously form with an increase in entropy (e.g., assemblies of proteins, cell membrane structures, and fibers) because in the process, disorder is transferred to the water molecules. Thus, the emergence of (highly-ordered) life is not a violation of the second law: “life reduces entropy locally while increasing it globally.” The author then goes on with some detail explaining another thermodynamic consideration: free energy. In the author’s words, free energy is the usable energy left over after the dispersed energy associated with entropy is subtracted from a systems total energy. “In the language of free energy, the second law is restated this way: At constant temperature, a system tends to decrease its free energy until, at equilibrium, free energy has reached a minimum. The second law tells us that useful energy will become degraded, and eventually we will only be left with dispersed, unusable energy.” In the following statement, the author succinctly hones in on how necessity and chance are reconciled in the spontaneous emergence of life: “The concept of free energy captures the tug-of-war between deterministic forces (chemical bonds) and the molecular storm – or in other words, between necessity and chance, in one elegant formula, F = E – TS.”
Where did all this free energy come from that sustains life on earth? “The big bang started out as pure energy and very little entropy “(a singular point). Shortly after the big bang, new particles were formed from this featureless energy (energy congealing is the phrase used by the author): quarks, electrons, muons, neutrinos, photons, etc. Chaos was created and entropy increased as free energy was degraded. After 300,000 years, the universe cooled down and the first protons and neutrons were formed when three quarks combined resulting in a release of energy. Protons and neutrons collide and stick to form nuclei further releasing energy which increased the entropy of the surrounding even as the entropy of the system decreased. As the universe cooled down further and became less dense, no nuclei with a greater mass than hydrogen and helium could form. Gravitation forces then exerted its influence as more dense regions of the ensuing universe attracted more atoms. As the nebulae grow into giant systems, it started to collapse under its own weight, the core got denser and hot enough to initiate nuclear fusion to create heavier nuclei all the way up to iron. “Hydrogen and helium were cooked into heavier elements, and stars were born.” Energy in the form of heat from nuclear fusion reaches the earth in the form of free energy that atoms and molecules can absorb. In a nutshell: “As free energy is dissipated, and the entropy of the universe increased, new structures are born, from quarks to nuclei to atom to…life.” Toward the end of the chapter, the author concludes with the profound statement that living systems are open, tightly controlled, dissipative, near-equilibrium complex systems. Living organisms are open systems because they allow the flow of energy but dissipative because they consume highly organized, low entropy energy and produce highly dispersed, high-entropy energy. They are efficient users of energy because their processes are always near-equilibrium and do not involve high fluctuations in energy flow (when at equilibrium organisms are dead). Living organisms carry the necessary structures and tools to push thermodynamics to its limit and these structures “operate at the nanometer scale, the tiny scale of molecules. But what is so special about this scale that chaos can become structure, and noise can become directed motion?” That is the question for the next chapter.
READING NOTES
INTRODUCTION: WHAT IS LIFE?
What controls this collection of molecules into a life-giving machine? The author believes that the “force that drives life is chaos”.
“The fundamental goal of this book is to follow the discoveries of [these] scientists and to find out what it takes to turn a molecule into a machine; and many molecular machines into a living cell.”
D’Arcy Wentworth Thompson (1917), a British biologist and mathematician, contended that “the structure of the living organism was the necessary result of mathematics and physics”.
Life is driven by the interaction between chance and necessity: “As we enter the microscopic world of life’s molecules, we find that chaos, randomness, chance, and noise are our allies. Without the shaking and rattling of the atoms, life’s molecules would be frozen in place, unable to move. Yet, if there were only chaos, there would be no direction, no purpose, to all of this shaking. To make this molecular storm a useful force for life, it needs to be harnessed and tamed by physical laws and sophisticated structures – it must be tamed by molecular machines.”
The chaos of the “random motions of the atoms in our bodies” are an “afterglow of the creation of the universe, big bang. The big bang created a universe full of energy, and, eventually, it created stars like our sun. With the sun as intermediary, the energy of the big bang shakes the atoms of our cells – making life on Earth possible.”
By the end of this book, whether the reader likes it or not, it would have made a complete argument for chaos as the life force, “tempered by physical law”.
CHAPTER 1 – THE LIFE FORCE
· “All life started as a circle dance of molecules billions of years ago.”
· “The author states that humans and other living beings are not sources of energy” but “consumers of energy”. In large part that is true but manual labor has been used for a long time to modify our environment.
· This chapter discusses how the discourse on what constitutes life has evolved over the ages beginning from ideas put forth by Greek philosophers. For hundreds of years, the debate about what constitutes “life” has centered on the concepts of “purpose and mechanism”. The author summarized the three most prominently held explanations for life, starting from the Greek philosophers to the early-19th century biologists:
o Animism:“assumes an overarching universal principle that determines the purpose of the entire universe”; “erased the clear distinction of the inanimate and alive”
o Vitalism: “assumes a special life force that distinguishes life from matter, thus reserving purpose for life alone; gratuitously introduced an unseen force and raised the additional question of how this force interacted with the body”
o Mechanism and atomism: “denies purpose altogether”; “seemed impotent to account for those of life’s activities that seemed to show clear purposefulness, such as growth and reproduction”
· It was Epicurus who ascribed something akin to the seemingly fatalistic [my word] concept of atomism as denying purpose altogether and believed that an atomistic explanation “needed a mixture of necessity and chance”.
· In “Medicine and Magic”, the author gives an account of how medicine, “the practical science of life”, has contributed to an increasingly scientific and quantitative knowledge of the workings of the human body that offered some concrete evidence related to the debate of what constitutes life. “Originally based on magic and faith-healing, medicine was put on a more rational footing by Hippocrates and other Hippocratic thinkers around the time of Aristotle”.
· Some of the other players that insinuated the observations of medicine to the debate include Galen who believed that a “pneuma” or “life spirit”, inhaled into the lungs, mixed with blood in the heart to produce “vital spirits” responsible for movement, generating heat when it mixed with the air. There was also Paracelsus whose belief in alchemy introduced concepts of chemistry to the debate.
· “Harvey’s mathematical reasoning had an enormous impact on the subsequent history of the life sciences: Life, like the rest of nature, could yield to quantitative analysis and, with it, careful experimentation”. William Harvey re-introduced and championed a more mechanical philosophy into the discussion of what drives life. He carried out a more quantitative method of understanding the workings of the human body questioning how the heart could possibly be the source of blood and where it eventually ends up, having calculated by multiplying the volume of the heart and the pumping rate that about 540 pounds of blood must be produced and must end up somewhere.
· Descartes also contributed ideas that supported the mechanical view of life: “The mind or spirit was to be the realm of the soul and the divine, while the body was pure machine”.
· This was the level and flavor of discourse that helped usher in the Scientific Revolution: “The mechanical worldview, the revival of atomism, and the combination of rational examination and experiment were the foundation for one of the most influential periods in the history of science, the scientific revolution, which lasted from the late sixteenth to the eighteenth century.”
· Galileo Galilei (1564 – 1642) and Isaac Newton (1642 – 1726) were the major players of this period. Both of these men were atomists and used experiment and reason to investigate nature. For instance, Newton believed that matter is composed of small hard particles.
· This more mechanical and atomistic view emerging during the scientific revolution helped propel the pursuit of instruments (with help from improvements in the understanding of optics) to study the living world, i.e. the microscope being one of the most important. It was then that Robert Hooke (1635 – 1703) and later Antonie Philips van Leeuwenhoek (1632 – 1723) first visualized cells but neither understood that they were looking at the fundamental unit of all living things. Hooke’s and others’ further observations further convinced of the mechanical nature of living things.
· Another medical doctor and philosopher, Julien Offray de la Mettrie, contributed to the discourse based on his experiences with the injured as a medical office to the French Guards. In his most popular work, L’homme machine, de la Mettrie concluded that organisms function as a result of their physical and mechanical make-up based on two observations:
o “the functions of the body and mind could be greatly altered by physical influences and therefore could not be independent of them”
o “living tissue, such as muscle, could move on its own, even when removed from the body”
· On the question of “Animal Heat”, the first commonly held belief, held even by Harvey himself, was that the heart was the source of bodily heat. Before Harvey’s time, Galen had correctly suggested a relationship between food and hear and had observed that both fire and life die in the absence of air, deducing that discovering why flames are extinguished in the absence of air may lend some answers to how the heat in animals rely on respiration.
· This belief was challenged by observations of animals that remain alive even though they are cold, e.g frogs by van Helmont. Van Helmont put forth the idea that heat was a product of chemical processes in the body and not its driver.
· Robert Boyle (1627 – 1691), John Mayow (1641 – 1679), and Robert Hooke showed that air is somehow involved with both fire and respiration and their production of heat.
· Lavoisier, father of modern chemistry, thinking that heat or fire is an element, carried out studies on heat in a complicated experiment done in the peak of winter to prevent the incursion of heat from the surrounding. He and Laplace found that “breathing and combustion generated roughly the same amount of heat for the same amount of carbon dioxide released. It wasn’t until the early 19th century that Benjamin Thompson correctly showed that heat is a form of energy.
· The birth of modern biology in the 19thcentury ushered in new methods and new ideas for investigating the “self-sustaining, self-organizing activity” basic attribute of life. In the field of embryology, the thinkers were divided along the lines of preformationists and the epigenesists:
· “Preformation was the idea that every living being had to be preformed in the egg or sperm.”
· “Epigenesists claimed that unformed matter was shaped into a complex living being during embryonic development.”
· Teleomechanistic and vitalist views (late 18thto mid-18th century) Immanuel Kant and biologist Johann Blumenbach came up with teleomechanism as a new way to combine ideas from the mechanical and the vitalistic points of views, espousing the idea that a vital force, separate from the organism, is a “result of its special organization and structure”. According to the author, this “view of self-contained special forces in organically organized bodies helped shape biology into an autonomous science”. These vital forces were identified by German biologist Kielmeyer as “sensibility, irritability, reproduction, secretion, and propulsion”. The teleomechanistic views of Kant and Blumenbach led to the development of the cell theory, the idea that all living organisms are composed of fundamental units called cells.
· In de la Mettrie’s view, however, irritability is evidence of the purely mechanistic basis for life. The study of irritability gained traction using new methods of applying electricity to animal parts (Galvani and his severed frog legs experiment was noted by the author as the iconic image of this era). These experiments and observations suggested that electricity could be the vital force propounded by many believers.
· Mid-19th century revival of the mechanistic view driven by the work of Charles Darwin (1809 – 1882) who “destroyed teleology” and Hermann von Helmholtz (1821 – 1894) who “vanquished the vital force”.
· Before Helmholtz, there was Robert Mayer who put forth ideas on the conservation of energy based on biological observations noting that energy and matter can only be converted from one form or another but ‘creation of either one or the other never takes place’.
· Helmholtz’s dismissed any utility of the vital force theory stating that its presence implies the possibility of a perpetual machine that can generate energy from nothing. Instead, he suggested that energy must be conserved beginning with the assumption that “matter was made of pointlike particles, interacting through forces depending only on the distance between the particles”. Helmholtz’s experiments showed that “all the hallmarks of being alive, from animal heat to irritability – had to occur within the energy budget prescribed by the physicochemical world”. These experiments”
o Showed that muscle movement is a result of a chemical process by comparing the chemical extracts from frog legs irritated by electricity and from those not subjected to electricity (some chemicals in the muscles irritated by electricity were transformed from being water-soluble to ethanol-soluble substances.
o Showed that the difference in energy between the latent of consumed food and latent heat of excrement correlated with the amount of animal heat. This experiment was also able to explain a 10% higher energy expenditure than can be accounted for by the amount of oxygen used in the oxidation from respiration noting that food already contains some oxygen. “If this additional oxygen was included, food energy perfectly matched animal heat plus energy of the excrements, and no vital force was needed.”
o Showed that the chemical energy was used to move muscles by showing that only electricity applied to the entire frog leg resulted in a temperature change (compared to electricity applied to only the frog leg without the nerve and just the nerve itself; it was believed that the nervous system supplied the vital force). To measure these very small temperature changes associated with muscle movement, Helmholtz built a thermocouple sensitive enough to measure down to 1/1000 of a degree.
· By the end of the 19th century, biology has returned to mechanism, with “all biological processes occurring within the framework of chemistry and physics”.
· Darwin and Mendel: From Chance to Purpose:
· The success of these mechanistic studies brought to light the fact that biology, physics, and chemistry must intersect to explain what gives life to organisms but did not answer the fundamental question issue of “purpose”:
· “By the end of the 1850’s, nobody could deny that explain life’s processes, physical, chemical, and mechanical forces had to be invoked. Yet mechanics seemed woefully insufficient to explain the ordinary complexity and purposefulness of life…How can complexity emerge from chaos?”
· Charles Darwin and Alfred Russell Wallace provided an answer when they developed the theory of evolution based on natural selection. In his Origin of the Species published in 1859, Darwin presented his observations and his arguments for natural selection as the driving force of evolution: variations within individuals of a given species that favor reproductive success lead to progeny, thus survival and propagation.
· Mendel’s work on genetics and inheritance answered the follow-up question of how those traits leading to survival and propagation are transferred to the offspring: “traits are inherited whole, and that traits from each parent can be combined in various ways in the offspring”. The fact that some of these individual traits from parents can be conserved, and not always blended, was crucial to Darwin’s theory: “Only traits that could be passed on whole to the next generation could spread through a population and explain the emergence of a new species. If traits were blending, any new traits would soon be blended back into mediocrity”.
· The next issue to resolve is the question of what gives rise to these variations.
CHAPTER 2 – CHANCE AND NECESSITY
· “Until the end of the nineteenth century, everybody believed that randomness had no place in any explanation of the world…The consensus was that if something happened by chance, it only seemed that way because of our ignorance of all the circumstances.”
· Pascal’s triangle can be used to determine how many times you can choose a certain number of items (k items) out of n available items. This number can also be calculated using the binomial coefficient expression: n!/(n-k)!k!
· “Statistics has been called the theory of ignorance.” “Statistics provides the clues to understanding the underlying regularities or the emergence of new phenomena arising from the interaction of many parts.”
· Laplace’s central limit theorem: “any measurement that depends on a number of random influences tends to have errors that follow the normal distribution”.
· Charles Darwin’s cousin, the mathematician Francis Galton, applied Quetelet’s ideas (“how the error law, the normal distribution, and the central limit theorem governed almost everything”) to a wide range of biological phenomena: heights, masses of organs, and circumferences of limbs and found that they all follow a normal distribution.
· Galton discovered “regression toward the mean” wherein the offspring of an outlier parent (e.g. height) takes on a characteristic that brings their combined numbers closer to the mean or the average (an extremely tall father tends to have shorter offsprings).
· Galton also discovered the coefficient of correlation, a statistical measure of how two different variables are still statistically linked or correlated. “A correlation is a hint of connection, no a proof.”
· Mendel used statistics to develop the laws of heredity.
Randomness and Life: Three Views
· Randomness: Quetelet’s and Galton’s work in biology à existence of atoms, statistical and quantum mechanics àmolecular evolution and the role of mutation
· D’Arcy Wentworth Thompson (1860 – 1948)
o “Cell and tissue, shell and bon, leaf and flower, are so many portions of matter, and it is in obedience to the laws of physics that their particles have been moved, molded, and conformed.”
o Thompson believed that the why and how of many phenomena of life and life itself can be explained given enough understanding of the complexities involved. “Invoking chance, God, or any extraneous life principle when met with ignorance was a cheap trick…to keep us from doing the hard work of finding the true causes”.
· Pierre Teihard de Chardin (1881 – 1955)
o Believed that life events happen due to a higher purpose and worked to reconcile science and religion.
o Saw evolution as a process toward a more and more complex and sophisticated form of life akin to God, embracing evolution but still relying on the existence of a higher purpose.
o Saw the connection of physics and biology in the cell
· Jacques Monod (1910 – 1976)
o The main premise of his belief is that the beginning of life is an improbable event but once it happened, evolution took over.
o Placed a high importance on the role of chance and randomness.
· The two dichotomies of how life may have come about: (see Figure 2.2)
o Dichotomy of mechanics (“mere physics”) versus higher forces (life forces, the soul)
o Dichotomy of chance and necessity
· Kinetic Theory à Laws of Thermodynamics àStatistical Mechanics àQuantum Mechanics
· The physicists lie within the intersection of mechanics (physical forces) and necessity but with the development of the kinetic theory which evolved and broadened into the Laws of Thermodynamics, they finally found a way to incorporate and tame randomness into their efforts to explain (and predict) the properties of matter based on the existence of atoms. The Laws of Thermodynamics became Statistical Mechanics when physicists “tamed randomness” with well-defined probability distributions developed by averaging over large numbers the random motions of atoms.
· “Statistical mechanics is the science of averaging large numbers of randomly moving molecules to arrive at precise macroscopic laws.”
· Qunatum mechanics came into the picture in the early 19th century replacing the “iron-clad model of necessity, classical physics” with a “fundamentally statistical picture of nature”.
· Meanwhile in Biology:
· Chromosomes (bundles of DNA) and their duplication during cell division were known by 1882 but it was not until 1900 that a connection was made between chromosomes and Mendel’s hereditary traits.
· By 1909, genetic experiments were being conducted on fruit fly drosophila by Thomas Hunt Morgan (1866 – 1945). Morgan discovered that traits are not independent as Mendel thought but are linked suggesting that “traits were contained in some kind of linear arrangement on chromosomes with nearby traits more likely to be inherited together. The mixing of traits was assigned to a crossing-over of linear molecules.”
· By 1920, it was clear that hereditary information was contained in the linear arrangement of the chromosomes. In 1926, Joseph Muller discovered after years of experimentation and using a controlled dose of x-ray that radiation increased the probability of new genetic traits being created due to mutations. This correlation was later refined with the help fo Max Delbruck and they subsequently showed that the mutation rates depend on temperature and x-ray dose.
· In the words of the author, this sequence of events during the first half of the 20th century illustrate how “previously mysterious biological processes, such as heredity and variation, became connected to measurable physical (molecular) entities”. “Helmholtz contribution was restrictive; “it subtracted vital forces from the list of possibilities”.)
· Erwin Schrodinger’s “What is Life” book: Schrodinger got a hold of the green book published by Delbruck et al and made some deductions:
· If x-rays were strong to ionize one atom out of a thousand, mutations would occur with near uncertainty – from this Schrodinger assumed this entity must be one thousand atoms large and therefore about 3 nm cubed. (Did not take into account what may have been unknown back then that it was radicals that caused bond-braking and they can travel farther than 3 nm cubed).
· Genes must be molecules due to their stability despite the elevated conditions in the body, molecules that are able to withstand the thermal motions within the cell. To hold a large amount of information, this “crystal” had to be aperiodic or non-repetitive.
· (We now know of course that the genetic material is an “aperiodic” polymer called DNA).
· To reconcile the interplay between necessity, laws of nature, and randomness, the author offers the following statement as a preview of the next chapter: “Life can best be understood as a game of chance – played on the chessboard of space and time with rules supplied by physics and mathematics.” These games begin at the level of the atoms.
CHAPTER 3 – THE ENTROPY OF A LATE-NIGHT ROBBER
· The author starts off this chapter by asking the following questions:
o How do atoms and molecules assemble into a flower and a human?
o Where do we cross the threshold from lifeless atoms and molecules to living organisms?
· To answer these questions, the author suggests starting from the fundamental building blocks of matter, atoms and molecules, and look at how these particles that are in constant motion come together to create ordered objects.
· In the late 1800’s, three scientists focused their research on this: Boltzmann, Maxwell, and Gibbs. The main focus of their study is how gaseous particles constantly in random motion result in macroscopic properties that follow the gas laws. To answer this, they developed statistical mechanics: “applying statistics to the chaos of atoms and molecules, they found that averaged over time and space, the randomness of atomic motion gives way to order and regularity”. Using statistical mechanics, Maxwell and Boltzmann showed that the range of particle speeds in a gas follow a normal distribution.
· The behavior of atoms and particles is governed by energy conservation, the strictest law of nature.
· Heat as a form of energy was the conclusion reached by Count Rumford after observing the kinetic energy of a metal cylinder boring a cannon was converted to heat.
· Maxwell, Boltzmann, and others developed kinetic theory invoking the existence of small particles such as atoms that are in constant motion.
· Atoms were first discovered by Robert Brown after he observed random motion of pollen grains now referred to as Brownian motion. Albert Einstein years later proved that the random motion of pollen grains was due to the random motion of much smaller particles.
· Physicist later on proved the existence of atoms and their constant motion using microscopes in the early 1900’s.
· The continuous motion of atoms and molecules is called thermal motion. Their speeds can reach up to 500 m/s, like speeds of airplanes. If were to scale down to the size of a molecule, it would be akin to being in a molecular storm. Even though molecules move very fast, they don’t travel far because they are in constant collision with other atoms and molecules.
· First law of thermodynamics: conservation of energy
· “Thermodynamics is the science that deals with thermal energy and is the macroscopic “sister science” of statistical mechanics. Thermodynamics is what emerges when we average the random motions of atoms using tools of statistical mechanics.”
· Not all types of energy are interchangeable. The convertibility of energy in a system of particles depends on the distribution of energies among the individual atoms. Temperature gives only a direct measure of the average kinetic energy thus macroscopic properties (or macrostates) cannot tell us much about the energies and speeds of individual atoms (or microstates).
· “Why are some types of energy more useful than others, specifically, why can some types of energy be converted while others appear difficult to convert, thus making them useless?”
· The concept of entropy is discussed in terms of microstates. A disordered arrangement where particles are randomly position is more probably because there are more microstates leading to this macrostate. The author makes the following comparison in terms of the entropy “content” of energy: gravitational energy is low-entropy energy while heat is high-entropy energy. “Friction and impact are great randomizers of energy.” “Energy that is completely organized, concentrated, and tidy is a rather artificial, low-probability situation.”
· This is the second law of thermodynamics: “in any transformation in a closed system, entropy always increases” (“energy becomes more and more dispersed and thus unusable”).
· Author’s statement of the second law of thermodynamics: “There can be no process whose only result is to convert high-entropy (randomly distributed) energy into low-entropy (simply distributed or concentrated) energy. Moreover, each time we convert one type of energy into another, we always end up overall with higher-entropy energy. In energy conversions, overall entropy always increases”.
· Entropy is a measure of the degree to which energy is dispersed (positional entropy ultimately only contributes to the total energy entropy because the energy of a particle is dependent on position but also on other modes of motions irrespective of position). Entropy is not just disorder.
· An example of the above is the difference in entropy between randomly stacked particles and orderly stacked marbles. In randomly stacked particles, the freedom of motion is actually reduced because some marbles are immobilized. In orderly stacked particles, the marbles have more freedom of motion. Randomly stacked particles therefore have higher positional entropy but lower energy entropy because of a narrower energy distribution. [USE IN 1B]
· Many biological structures that are highly ordered spontaneously form with an increase in entropy (e.g., assemblies of proteins, cell membrane structures, and fibers) because in the process, disorder is transferred to the water molecules.
· The emergence of (highly-ordered) life is not a violation of the second law. Entropy can be locally reduced but globally increased in a transformation. Also, there are examples of highly ordered structures that embody more entropy.
· “Life reduces entropy locally while increasing it globally.”
· The author on free energy:
o “Free energy, F, is the total energy E minus the product of temperature T and entropy S of the system (F = E-TS). Because entropy represents how much energy has become dispersed and useless, free energy represents that part of the energy that is still “concentrated” and useful (because we are subtracting the useless part, TS).”
o “In the language of free energy, the second law is restated this way: At constant temperature, a system tends to decrease its free energy until, at equilibrium, free energy has reached a minimum. The second law tells us that useful energy will become degraded, and eventually we will only be left with dispersed, unusable energy.”
o “The concept of free energy captures the tug-of-war between deterministic forces (chemical bonds) and the molecular storm – or in other words, between necessity and chance, in one elegant formula, F = E – TS.”
o “According to the second law, free energy will eventually be degraded and reach a minimum.”
· The Big Bang and where free energy on earth came from:
o “The big bang started out as pure energy and very little entropy “(a singular point).
o Shortly after the big bang, new particles were formed from this featureless energy (energy congealing is the phrase used by the author): quarks, electrons, muons, neutrinos, photons, etc. Chaos was created and entropy increased as free energy was degraded.
o After 300,000 years, the universe cooled down and the first protons and neutrons were formed when three quarks combined resulting in a release of energy. Protons and neutrons collide and stick to form nuclei further releasing energy which increased the entropy of the surrounding even as the entropy of the system decreased. As the universe cooled down further and became less dense, no nuclei with a greater mass than hydrogen and helium could form.
o Gravitation forces then exerted its influence as more dense regions of the ensuing universe attracted more atoms. As the nebulae grow into giant systems, it started to collapse under its own weight, the core got denser and hot enough to initiate nuclear fusion to create heavier nuclei all the way up to iron. “Hydrogen and helium were cooked into heavier elements, and stars were born.”
o Energy in the form of heat from nuclear fusion reaches the earth in the form of free energy that atoms and molecules can absorb.
o In a nutshell: “As free energy is dissipated, and the entropy of the universe increased, new structures are born, from quarks to nuclei to atom to…life.”
· Living systems are open, tightly controlled, dissipative, near-equilibrium complex systems:
o “The continual flux of energy is a fact of life – a fact that keeps living systems out of thermodynamic equilibrium. Equilibrium is the state in which all available free energy has been degraded and no usable energy remains. Equilibrium means death. Living beings must avoid equilibrium. As long as we are alive, energy continues to flow through us. In thermodynamics, systems through which energy and matter flow from and to the environment are called open systems.’
o In living systems, “what enters is not the same as what leaves the system. Living beings gobble up low-entropy energy, degrade the energy, and expel high entropy energy into the environment. We call such systems dissipative systems, because they continuously dissipate free energy into high-entropy energy.”
o “Life is a highly efficient process. Efficiency is best achieved when we do not stray too far from equilibrium, because large movements cause friction and, consequently, rapid degradation of low-entropy energy…By staying away from equilibrium, we stay alive. By staying close to equilibrium, we increase efficiency.”
· “Such a complex system as life can only work if its parts are designed to push thermodynamics to its limits. Life does not exist despite the second law of thermodynamics; instead, life has evolved to take full advantage of the second law where it can.”
· How can it do this? “Life’s engines operate at the nanometer scale, the tiny scale of molecules. But what is so special about this scale that chaos can become structure, and noise can become directed motion?”
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