Getting Down to Business
Economic metaphors help to better understand cell biology. In return cell biology teaches some first principles of economics. This “Little Big History” connects processes inside microbial organisms to processes of the global economy.
Human Nerve Cell: Astrocyte grown in cultureCells are really small. You will recall that the diameter of a single hydrogen atom is approximately 0.1 nm (nanometers—a billion times smaller than one meter). The smallest bacteria are about 150–250 nm in diameter. The bacterium E. coli, part of your intestinal microbiome, measures up at approximately 2 µm (micrometers or microns). Here we have moved up in the scale a thousandfold, from nanos to microns, from 10-9 m to 10-6 m.
To grok these jumps in orders of magnitude is no minor matter. Think of one nanometer as somehow equivalent to $1. Our hydrogen atom would cost about ten cents at the local supermarket. Fortunately, there is an abundance of hydrogen and it doesn’t take up a lot of shelf space. A single bacterium, the aforementioned E. coli at 2 micrometers, is available for a cool $2,000. Your gut contains trillions of such cells, so stock up. At the millimeter scale, we can actually see what we’re buying, if we look carefully. The price of a C. elegans, a 1-mm transparent roundworm used widely in genetic and neuroscience research, is going to cost you $1,000,000. A shopping cart full of food would cost you trillions of dollars.
Of course, this analogy is technically misleading—meters and dollars are not equivalent. The analogy, however, illuminates more than just the scale of size from nanometers to meters. It also reminds us that there is always an energetic cost in growing complexity. Bigger entities really are more expensive. Evolving complex cells require orders of magnitude more atoms, and orders of magnitude more energy, to create, maintain, grow, reproduce, and evolve. As we will explore below, there is always a cost.
The Central Bank of Chemistry
We begin with a review of some basic chemistry. Atoms—composed in the first order of protons, neutrons, and electrons—are the building blocks of chemistry. Most of the atoms in the Periodic Table of Elements were created by stellar fusion in giant, fast-burning stars. When these massive stars exhausted their fuel, they collapsed and blew up in supernovae. The remains of these supernovae then gave rise to new star systems containing the possibilities of complex chemistry. Our solar system is such a place—the material remains of a colossal star that died in a dramatic explosion over 8 billion years ago.
It took a lot of energy to fuse simple atoms—hydrogen and helium—into heavier atoms. The sun converts 4 million tons of matter into energy every second through fusion reactions that turn hydrogen into helium. The conversion of matter into energy is expressed in the iconic equation E = mc2. Converting a whole lot of energy into a wee bit of matter is how particle physicists interrogate the subatomic realm of matter at CERN and other particle accelerators around the world.
Chemistry follows different rules than nuclear physics. In normal chemistry, elements in the Periodic Table are indestructible. Atoms can and do join together to form molecules. Molecules can and do fall apart, but the atoms that constitute the molecule retain their basic identity before, during, and after these transformations. That identity—hydrogen, helium, oxygen, carbon, iron, and all the rest—is determined by the numbers of positively charged protons in the atomic nucleus along with an assortment of neutrally charged neutrons.
Chemistry is mostly about the affinities of electrons. As described by quantum mechanics, electrons exist in clouds of “probability space,” albeit in distinct orbitals, around a positively charged nucleus. Standing between the nucleus and the electrons is a whole lot of empty space and powerful magnetic fields.
Imagine a simple hydrogen atom—one proton and one electron—as a major league baseball stadium. Think of the proton as a baseball on the pitcher’s mound. The electron would be something smaller than a flea somewhere at the furthest reaches of the stadium; and this flea is moving at extraordinary speeds. The electron of a hydrogen atom covers about 2,200 kilometers per second in its frenetic orbit around the single proton nucleus of hydrogen. It helps to be really small if you want to travel at these speeds.
Look around at your immediate surroundings—books, chairs, tables, walls, floors, windows, computers, and your hand. Lots of reliably solid objects. Don’t think of matter that way. Instead, try to grok the magnetism of ecstatic electrons vibrating with their nuclei. It is this electromagnetism that gives us the illusion of a world of solid objects, when those objects around you are actually mostly empty space. Even when packed tightly in objects like rocks, atoms are always busy. While not alive, atoms are certainly animate, if that makes sense. On the atomic scale, nothing is inert and unmoving. Everything vibrates with intense activity.
There is a kind of electron law of supply and demand. Following their affinities, busy electrons are promiscuously exchanged and shared between atoms, joining together elements into new compounds. The electrons are looking for a place to rest that is not as frantic as where they just were. The logic of the outer electron orbitals determines if, whether, and how atoms combine into molecules and. Alternately, how molecules fall apart. Poor helium is inert, so stable, that nobody bonds with it. The rest of the Periodic Table, however, is capable of joining into molecules. It’s in the nature of the atoms of the right kind in the right conditions to form molecules.
When an electron leaps to another atom, the donor atom’s electromagnetic charge is reduced—making it more positive—while the recipient’s negative charge is increased. The participants in this electron exchange may be strangers passing in the night. As often as not, though, their newly found positive and negative valences create an instant bond between the two—opposites attract in an ionic bond. Electron transfer is one of the ways that atoms turn into molecules.
Sodium chloride (i.e., table salt) is the textbook example of such a molecule. The sodium atom (Na) loses an electron to chlorine (Cl). Na is now positively charged. Cl is now negatively charged. The two elements are bound together by their positive and negative attraction—an ionic bond.
Na + Cl → Na+ + Cl− → NaCl
Electrons can also be shared between atoms. This is called a covalent bond. The textbook example is water (H2O). In water the electrons from the two hydrogen (H) atoms come to orbit around the nuclei of both the oxygen and hydrogen atoms.
H2 + O → H2O
Sharing electrons creates a stronger and more enduring bond than the positive and negative attractions of ionic bonding. Complex molecules typically employ both kinds of bonds. The economies of chemistry are a series of limited partnerships (covalent bonding) and merger acquisitions (ionic bonding).
Some atoms, carbon for instance, are especially good at forming covalent bonds with other atoms. Life harnesses the chemical properties of the carbon atom to construct complex molecules. The formula for methane is one carbon atom bound to four hydrogen atoms (CH4). Having filled its outer orbital with the shared electrons from the hydrogen atoms, the carbon and hydrogen atoms are more stable and less reactive in the new molecular form.
Oxygen, on the other hand, is reactive by its nature. Oxygen is always out to dump an electron or two on its neighbors. When it can, oxygen is said to “oxidize” other atoms and molecules. This combustion can happen fast or slowly, spontaneously or induced. The mere presence of oxygen causes iron (Fe) to slowly rust.
2 Fe + 3 0 → Fe2O3
A candle, on the other hand, must be induced to burn with a match. The rapid oxidization of the wax generates heat and light. Both reactions are examples of combustion, though the oxidizing of iron is much slower. It is the same basic chemical process in all living cells, though not necessarily with oxygen as the reactive element. Other elements can also do duty. A key oxidation reaction process inside of complex cells is respiration. All chemical reactions export heat energy to the surrounding environment.
When oxygen reacts with methane, the methane is oxidized, forming carbon dioxide and water. This reaction gives off heat. It is exothermic.
Molecules greatly complicate the affinities and possibilities of electrons and their atoms. For instance, there are twenty different amino acids with a mean of 19.2 atoms per molecule. Amino acids combine by the hundreds to form proteins. A midsized protein might contain some 400 amino acids. This single protein molecule thus contains 8,000 atoms plus or minus—hence the nomenclature “macromolecule.” The elements involved are primarily carbon, hydrogen, oxygen, and nitrogen—held together by both covalent and ionic bonds. The geometry and intensity of these affinities determine how proteins fold into particular shapes that perform specialized cellular functions. Even the smallest single-cell economies contain many millions of proteins inside their cytoplasm.
This trade in electrons drives the economies of chemistry. Unlike human currency, the medium of exchange has intrinsic value. The Central Bank of Chemistry is backed by the Laws of Thermodynamics. Suffice it to say that some chemical reactions release energy to the environment—these are called “exothermic” reactions. And other chemical reactions consume energy from the environment—these are called “endothermic” reactions. Many do both, up and down energetic scales and embodied complexities. It takes a match to start a campfire (an endothermic reaction). The sustained combustion of the wood, however, is a net exothermic chemical process dissipating heat, light, and gases into the environment. If we include the entire energy life cycle of the tree from which the wood came, then we have a net endothermic event. It took orders of magnitude more solar energy to grow a bundle of firewood than the energy that is released in the fire itself.
Chemical complexity requires two things. First, it requires a source of energy in order to arrange atoms into molecules. Having created more complex molecules, it can also require energy to break them down. Second, it requires a heat sink, a place to discard disorder, a garage dump to dissipate energy. On the planetary scale, the cold of outer space is the Earth’s heat sink, even as the sun is our primary heat source. On the chemical scale, the local environment of the system will do just fine. Both the energy sources and the energy sinks are found in the surrounding environment of all complex systems. In all cases, energy is consumed from and released to the environment in order to create, maintain, rearrange, and break down molecules.
Electromagnetism is what holds the world together, at least the scales that matter most to humans. Technically, there are four fundamental nuclear forces—electromagnetism, gravity, strong nuclear force, and weak nuclear force—but at our biological scale electromagnetism does the work of normal chemistry. The electromagnetism of chemistry drives the energetic flux that animates life and the growth of complexity in the world around us.
The Central Bank of Chemistry is always depreciating its energy reserves, a fact that, on the macro-level of Big History, we can happily ignore for a couple billion years. We live on a tiny thermodynamic eddy in a universe where free energy is plentiful and complexity has the possibility of running up hill. The monetary policies of our planet are based on the sun, the deep cold of space, and the fundamental laws of physics. Investors can count on these as a reliable partner in terrestrial markets for at least 2 billion years.
The Currency of Life
The currency of cell biology is the ATP (adenosine triphosphate) molecule. ATP is an energy delivery system, each molecule a little packet of energy to be put to use in the continuous construction of the cell. Like money, ATP circulates throughout the economy of the cell. Unlike money, it needs to be reminted after each transaction. The molecular remains of spent ATP are quickly recycled to make more ATP. All forms of life—from bacteria to blue whales—use ATP to energize their creative dynamic.Joining amino acids together to make a protein takes about five ATP molecules for each bond. Constructing a modest-sized protein of 400 amino acids would consume about 2,000 ATP molecules. From there the numbers quickly become astronomical. Protein construction occurs at a frantic pace inside a cell. When we add all the molecular activities going on inside a simple cell, we’re looking at hundreds of thousands or even millions of ATP molecules consumed per second. A human typically consumes about its weight in ATP molecules every day, but at any given moment, there are only about 250 grams of ATP in the human body. ATP is continuously consumed and recycled inside the economy of a single cell at a rate that dwarfs daily foreign currency transactions in our human economy (ca. $4 trillion per day is exchanged via the international SWIFT system).
The continuous minting of ATP requires chemical energy—as mandated by the Universal Central Bank (see energetics in chapter 2). Cells take in food from the environment and then break down this food into smaller usable molecules. Electron transfer reactions then turn these small molecules, primarily glucose, into energy for cell construction.
Cells, moreover, have figured out how to store electrical energy by turning membrane barriers into batteries. In order to transport food energy in and waste out, cell membranes need to also be selectively permeable. This is achieved by protein structures embedded in the otherwise impermeable lipid membrane. One such structure oxidizes hydrogen atoms, removing the electron and using the energy therefrom to pump the remaining proton across the membrane.
Normal chemistry, we observed, was about the affinities of electrons. You don’t find unattached protons floating around on Earth, as they would immediately grab an electron from its neighbor and revert into a hydrogen atom. But in cell biology protons are the key to storing and utilizing potential chemical energy. If you collect enough protons on one side of the membrane, you’ve got a battery.
The positive valences of the protons on one side of a membrane create a powerful electromagnetic field that drives the ATP synthesis and other cellular functions. How strong? The electromagnetic valence across a mitochondrion membrane would scale to 30 million volts per meter, equivalent to a lightning strike. Fortunately, this occurs not at the scale of meters and megavolts, but at the scale of nanometers and millivolts. This is the vital force that drives ATP production and the prodigious biochemistry of all life. The molecular machines that drive this process are not found anywhere in inanimate nature, except as mimicked in human technology and engineering.
The Business Models of Life
Life excels at capturing and concentrating energy, harnessing the chemicals in its environment to grow and reproduce. It does so both by evolving new efficiencies, like enzymes that speed up and channel chemical reactions, and by increasing overall energy intake.
Life began about 4 billion years ago as single-cell prokaryotes, which come in two families, bacteria and archaea, distinguished by their membranes and other features. Prokaryotes share many biochemical pathways, including the use of ATP and DNA. Prokaryotes have no nucleus or other membrane-bound organelles. Eukaryote cells, on the other hand, have a nucleus and organelles and are usually much larger and morphologically more complex than prokaryotes. All plants and animals are eukaryotes.
Life probably first got hold in alkaline hydrothermal vents on the ocean floor, an environment rich in energy and chemical possibilities. Somehow this chemical caldron boot-strapped itself into life, mastering metabolism, membranes, and memory. Early prokaryotes reproduced, evolved, and spread around the planet, developing enormous genetic diversity. Along the way the bacteria and archaea developed all the major chemical metabolic pathways. Their biochemical ingenuity allowed them to harvest more energy and matter from increasingly diverse biomes on our restless planet.
Genes are the architectural plans for cell construction and replication. Without genes, life has no memory of itself and no capacity to “compute” more life. Prokaryotes divide into clones, but they also exchange genes through lateral transfer with their neighbors. Genes can be exchanged through viral transfer or simply proximity as prokaryotes give away and pick up DNA segments. The bacterium E. coli, for instance, has only about 4,000 genes. The metagenome of all E. coli bacteria, however, may contain 18,000 genes. Indeed, the prokaryotes need not be of the same species to share genes. Keeping a lot of useless genes around is expensive, so bacteria are quick to discard unused genes and to try out new genes that might be useful. The genomic situation between prokaryotes is so confused that some biologists think of all prokaryotes as a single species. “Simple” bacteria and archaea created the world’s first global economy of staggering complexity with its own world wide web of information sharing.
The First Agricultural Revolution
Human agriculture is all about harvesting energy from the sun through domesticated plants and animals. Bacteria figured out how to do this some 3.5 billion years ago when they invented photosynthesis. This ability to tickle a photon from the sun and turn it into food allowed an exponential growth in life beyond the finite chemical and thermal potential energy of our young planet. In the process, bacteria sculpted rocks, laid down huge sedimentary deposits, changed the oceans, and transformed the environment. Photosynthesis enables plants to breathe in carbon dioxide, soak up water, and exhale oxygen in order to create carbohydrate food molecules to fuel cell growth.
Carbon dioxide is one of the greenhouse gases implicated today in anthropogenic global warming. Two billion years ago, the reduction of carbon dioxide in the atmosphere presented a different dilemma. A billion years after photosynthesis began, oxygen levels began to rise in the atmosphere. A reduction in carbon dioxide levels and and an increase in oxygen levels in the atmosphere resulted in global cooling. The Earth was soon covered with ice—like a giant snowball—in what is referred to as the Great Oxidation Event.
Those prokaryotes that could not adapt to the new oxygen-rich environment retreated into the anaerobic muck. Others evolved membranes that could resist oxygen and later harness its power through respiration, greatly magnifying the energy production power of the cell. It is not clear whether any lineage of prokaryotes ever actually went extinct, though the environments in which anaerobic prokaryotes can thrive changeddramatically as oxygen became more abundant. With photosynthesis and later respiration, single-cell life had a new and practically unlimited source of energy fueling a Great Radiation of life in the terrestrial oceans.
Photosynthesis is the miracle machine that energizes all life. It didn’t start out that way, but in the ensuing eons, the baroque varieties and abundance of life were and still are founded on this molecular legerdemain. Many prokaryotes still make their living by harvesting chemical energy in their environment, as all prokaryotes did before photosynthesis, but they are a small part of the Gross Primary Productivity (GPP) of our planet’s annual biomass today. At the bottom of the food chain and the energy economy of our planet is photosynthesis—a process of transforming carbon, water, and sunlight into life more abundant.
Prokaryotes still reign today. Their biomass probably exceeds that of all eukaryotic life. Prokaryotes have an incredible capacity to set up shop inside and on top of every surface, climate, geography, and creature on this planet. We are here today as their descendants, guests, and servants; but we—the royal eukaryote “we” including all plants, animals, and fungi—are also singularly different from the prokaryotes.
The First Industrial Revolution
Eukaryotes appeared about 2 billion years ago. Unlike prokaryotes, they have a differentiated, membrane-bound nucleus and specialized organelles—mitochondria, chloroplast, Golgi apparatus, endoplasmic reticulum, a complex cytoskeleton, and more. Eukaryotes mostly engage in sexual reproduction. And while prokaryotes need not die—their daughter cells continue as clones—most eukaryotes have preprogrammed senescence built into their DNA. Eukaryotes are usually orders of magnitude larger than prokaryotes.
The story of the first eukaryotes—the lineage we share with all fungi, plants, and animals—is astounding science, the stuff of fairy tales, really. It is a story told in bioinformatics and the comparative analysis of microbial genomes, knowledge and knowhow only recently acquired by scientists. Once upon a time—long, long ago—some microbes made their living by eating other microbes, which turns out to be very nutritious. This was, and still is, pretty normal for microbes and other living things. The technical term for this phenomenon is “heterotrophy”—which means “other feeder”—in contrast to the autotrophy of photosynthesis. Every day we eat other living things—three meals a day perhaps and a few snacks in between. One day, though, something strange happened that apparently only successfully happened once or twice in the history of the planet. A single-cell archeon swallowed some bacteria for breakfast, but the breakfast didn’t digest.
Normally, enzymes break down the captured microbe into bite-sized food molecules. Not this time. Instead, breakfast decided that the cytoplasm of the predator cell was a good place to live and start a family. As kids, we feared that a swallowed watermelon seed might grow into a new watermelon inside our stomachs. This is kind of what actually happened 2 billion years ago in the great microbial leap forward.
The initial acquisition and merger between the archeon and the bacterium created deadly competition inside the cell. Presumably this has been tried and failed a multitude of times, leaving no geological trace or contemporary intermediaries. The successful merger of two microbes— endosymbiosis—was something quite singular in evolution. It only successfully happened once, maybe twice, in the history of our planet. The ur-eukaryote—the grandmother cell of all fungi, plants, and animals—somehow developed a complex cell with differentiated organelles. The ur-eukaryote acquired and domesticated a parasite, resulting in an exponential evolutionary jump in the flux of energy, matter, and ingenuity.Over time, the newcomers evolved into organelles—mitochondria and chloroplasts. The endobionts started getting rid of excess DNA, keeping only genes necessary for their own reproduction inside the host’s cytoplasm. Some of these discarded genes were picked up by the host cell and kept inside its newly formed nucleus. Sexual reproduction mixed things up more.
The new lineage of eukaryotes evolved into new morphologies and possibility spaces. With the radiation of eukaryotes, the quantity of organized information—in the size and varieties of proteins and in the number of DNA base pairs inside cells—begins to grow exponentially. The average size of proteins increases dramatically as we move from archaea and bacteria to eukaryotes. Eukaryotic complexity can also be crudely measured in the amount of DNA that rapidly accumulated inside the nucleus of cells at the time of the Great Radiation of eukaryotic life 2 billion years ago.
Breakfast turned into a houseguest that wouldn’t leave and kept getting more plentiful as it reproduced. To keep up with its own reproduction, as well as the parasites reproducing in its cytoplasm, the competition had to turn into cooperation and mutual benefit. A house divided cannot stand. Over time, the sons and daughters of the ur-eukaryote figured out how to turn competition into cooperation and then reproduce that know-how. The parasites—powered by photosynthesis and chemistry—began to share ATP with the host cell. Breakfast turned into a parasite, which then turned into a symbiont living inside the cell.
The exponential growth in information-ingenuity in the Great Radiation of eukaryotic life required an exponential increase in the flux of energy-matter. Sexual reproduction was one of the technological innovations that helped solve this problem. Sex is how eukaryotes explored adjacent morphological possibilities in the environment. The chloroplast and mitochondria organelles inside the eukaryote cells became the energy engine of evolution. The Central Bank of Chemistry was able to dramatically grow the supply of ATP in the economy of cells, energizing the great microbial leap forward.At first, the new lineage of eukaryotic microbes was made up of single-cell creatures known as protists. They come in plant-like, animal-like, fungus-like, and mixed-up varieties. Chlamydomonas reinhardtii, for instance, is a single-cell alga that reproduces both sexually and asexually, has motility and heterotrophy, and behaves like an animal but is also capable of photosynthesis like a plant. Most protists vary in size from 10 to 100 µm (i.e., thousands of times larger than the average prokaryote).
Unlike prokaryotes, which are biochemically complex but morphologically simple, the newly incorporated eukaryotes grew in size and morphological complexity. Sexual reproduction within distinct lineages of eukaryotes and the inevitability of death gave rise to a dramatic evolutionary radiation of diverse kinds in the history of our planet.
Eukaryotes took cooperation-competition to new levels by forming multicellular organisms with specialization and divisions of labor. The diminutive, ever-adaptive prokaryotes in the environment, of course, went along for the evolutionary ride with the big, new eukaryotic creatures. Bacteria and archaea are an essential component of our development and health, and we contain multitudes in our bodies. Sometimes, of course, bacteria cause disease and death, but we are learning that early and frequent exposure to the bacteria in the environment is essential to developing a healthy immune system. We did not evolve to grow up in an antiseptic environment. Eukaryotes evolved through natural selection into the marvelously diverse and complex fauna and flora that amaze us in nature today. And it apparently had a singular origin the early history of life.
The Whole Economy of Nature
In On the Origin of Species, Charles Darwin wrote of “the whole economy of nature.” We have extended the metaphor of “economy” to the level of single-cellular life. Economics and biology have come a long way since Darwin first used this analogy. Single-cell prokaryotes and eukaryotes have their own laws of supply and demand involving electron markets and the currency of ATP. Specialization and the division of labor were already nascent in the biochemistry of hunter-gatherer prokaryotes. The invention of photosynthesis was a kind of agricultural revolution, dramatically increasing the energy that could be harnessed to support the growing economies of life. The microscopic prokaryotes also created a global trade in DNA fragments, which continues to this day, aided now in their spread by human trade and travel. Specialization and division of labor took a giant leap forward in the industrial revolution of eukaryote lineages. Multicellular organisms took this profligacy to new heights.
Cells—big or small—maintain their identity through inconceivably frenetic activity. Trillions of chemical cascades occur every second inside each cell. Even the smallest bacteria contain many thousand different types of protein molecules of. To maintain such complexity, cells need to take in matter and energy and dispose of waste. Cells needs to defend themselves from predation and harm, while seeking out new sources of energy and matter from their environment so they can exist, grow, reproduce, and complexify. This is how economies also function.
There are about 37 trillion cells in a 70-kilo human body (and approximately an equal number of prokaryotes—weighing about 3 kilos). And though you may experience yourself to be unified and coherent, at times even calm and relaxed, the incomprehensible frenzy of each cell in your body continues throughout the nights and days of your life.
Life is an energy-matter and information-ingenuity processing system. The flux of energy-matter is guided by information-ingenuity. Life has a built-in telos—which is to survive, grow, and reproduce life that is more abundant, more diverse, more extravagant. Information is passed on to descendants in the code of DNA, which is then read into protein structures that function within this vast biochemical cauldron. The code choreographs the marvelous dance of energy, matter, and ingenuity in the great flux of emergent complexity called life.
It begins and ends with energy density flows. Selectively taking molecules in the environment and turning them into the molecules of life requires a lot of energy. Cells achieve a temporary homeostasis inside their membranes through a dynamic chemical-energetic disequilibrium with the outside environment. If you don’t understand bioenergetics and bioinformatics, you don’t really understand the economy of a cell, let alone the whole economy of nature. If you don’t understand energetics and informatics, you also don’t understand human economies. The universal formula for creating, maintaining, growing, and evolving complexity is energy, matter, and ingenuity.
By changing scale, we can shift from inside a single cell to the economy of many individual cells interacting. The latter—individuals interacting—occurs in the form of microbial ecosystems and is also manifested in the rise of multicellular organisms. At this point I don’t know how the economic metaphor best applies. In the context of cell biology, what counts as an individual or a corporation? Where should we draw the line between microeconomics and macroeconomics? I don’t know. But certainly, like economic markets, cell biology and cell ecologies are emergent phenomena. Many actors buying and selling make the market. One cannot predict market trends based on a single corporation or individual. Similarly, one cannot really understand the behavior of a single cell by studying a single protein, let alone a single atom. Multicellular organisms and microbial ecosystems add orders of magnitude more complexity to the level of analysis.
Cell biology and economic markets are examples of complex adaptive systems. The economy of cells, however, is more than just a metaphor for economics. Complexity theory—and its cousin, chaos theory—allows us to discover common patterns in disparate natural phenomena. Star formation, cell biology, genomics, ecology, earthquakes, floods, neuroscience, and economic markets turn out to share common patterns.
Applied Big History is an attempt to build those connections between domains and disciplines—in this case, to learn how the physical and biological patterns appear also in economics and finance. In short, markets and cells are bottom-up, disturbed processes, involving countless agents, products, services, and technologies, all utilizing energy, matter, and ingenuity flows to maintain and grow complexity. Markets and cells are all about process and change. And like economic markets, cell biology is stunning to behold—trillions of atoms organizing themselves in microseconds and over eons into dynamic, self-replicating, and evolving flows of energy, matter, and information.
 Elise Bohan et al., Big History (New York: DK, 2016), 58.
 Jefferson Lab (2018), https://education.jlab.org/qa/electron_01.html.
 Marie-Paule Lefranc and et.al., “Amino Acids,” International Immunogenetics Information System (2015), http://www.imgt.org/IMGTeducation/Aide-memoire/_UK/aminoacids/abbreviation.html.
 Ron Milo and Rob Phillips, 2015, http://book.bionumbers.org/how-many-proteins-are-in-a-cell/.
 “Adenosine Triphosphate,” Wikipedia (2018), https://en.wikipedia.org/wiki/Adenosine_triphosphate.
 Nick Lane, The Vital Question: Energy, Evolution, and the Origins of Complex Life (New York: W.W. Norton & Company, 2015), Kindle 1104.
 Ibid., Kindle 2869.
 Net Primary Production (NPP) is defined as the Gross Primary Production (i.e., all photosynthesis) minus the water content. Vaclav Smil, Energy in Nature and Society (Cambridge, MA: MIT Press, 2007), 69.
 Olivia Judson, “The Energy Expansion of Evolution,” Natue Ecology & Evolution 1 (2017).
 Ed Yong, I Contain Multitudes: The Microbes within Us and a Grander View of Life (New York: HarperCollins, 2016).
 Eva Bianconi, Allison Piovesan, and et al., “An Estimation of the Number of Cells in the Human Body,” Annals of Human Biology 40, no. 6 (2013). Ron Sender, Shai Fuchs, and Ron Milo, “Revised Estimates of the Number of Human and Bacteria Cells in the Body,” PLOS Biology (2016).
Jefferson Lab (2018). https://education.jlab.org/qa/electron_01.html.
“Adenosine Triphosphate.” Wikipedia (2018). https://en.wikipedia.org/wiki/Adenosine_triphosphate.
Bianconi, Eva, Allison Piovesan, et al. “An Estimation of the Number of Cells in the Human Body.” Annals of Human Biology 40, no. 6 (2013): 463-71.
Bohan, Elise, Robert Dinwiddie, Jack Challoner, Colin Stuart, Derek Harvey, Rebecca Wragg-Sykes, Peter Chrisp, et al. Big History. New York: DK, 2016.
Judson, Olivia. “The Energy Expansion of Evolution.” Natue Ecology & Evolution 1 (2017).
Lane, Nick. The Vital Question: Energy, Evolution, and the Origins of Complex Life. New York: W.W. Norton & Company, 2015.
Lefranc, Marie-Paule, and et.al. “Amino Acids.” International Immunogenetics Information System (2015). http://www.imgt.org/IMGTeducation/Aide-memoire/_UK/aminoacids/abbreviation.html.
Milo, Ron, and Rob Phillips. “Cell Biology by the Numbers.” Garland Science, 2015.
“Proteins.” Wikipedia (2017). https://en.wikipedia.org/wiki/Protein.
Sender, Ron, Shai Fuchs, and Ron Milo. “Revised Estimates of the Number of Human and Bacteria Cells in the Body.” PLOS Biology (2016).
Smil, Vaclav. Energy in Nature and Society. Cambridge, MA: MIT Press, 2007.
Yong, Ed. I Contain Multitudes: The Microbes within Us and a Grander View of Life. New York: HarperCollins, 2016.