LifeAscending

• Fantastic! Another new favorite author. Great big picture overviews of biology with a chemists perspective.
• Life itself turned our planet blue and green. Photosynthetic bacterial cleansed the air and sea and filled them with oxygen. This new and potent source of energy powered larger life forms.
• Until recently there have been two paths into the past: fossils and genes. Both have their pros and cons. There are now powerful methods that go beyond these and this book is in part a celebration of them.
• Its a joy to be alive at this time, when we already know so much, and yet still look forward to so much more.

NowIsDifferent

• Life emerged 3.8 billion years ago. Bacteria dominated our planet for 2.5 billion years before the first complex organisms appeared.
• Chemistry => that life had to emerge quickly. Chemical reactions must happen rapidly or not at all. If a reaction takes 1000 years then the reactants will simply dissipate unless they are continually replenished by other faster reactions.
• The origin of life is not the great mystery that it is sometimes made out to be. Life emerges, perhaps almost inevitably from the turning of the globe.
• Miller-Urey experiment, amino acids forming is "primordial soup" after electrifying a simple mixture of gases. Over time this has fallen out of favor. Ancient rocks make it clear that the earth never was rich in methane, ammonia and hydrogen. The soup idea was rescued by the detection of abundant organic molecules in space (comets and meteorites)
• The origin of life is the origin of replication. A corpse cant be brought back to life by electrocuting it repeatedly.
• The molecules in food want very much to react with oxygen. The slow-burning combustion that sustains us all, is when hydrogen stripped from food reacts with the oxygen to release all the energy we need to live. This is the real problem with the soup. it is themodynamically flat. Nothing in the soup really wants to react. There is no disequilibrium, no driving force.
• Population densities in the the deep-sea vents rival a rain forest despite being powered by the vent exhaust rather than the sun.
• Sulfur bacteria can extract hydrogen from the vents and attach it to carbon dioxide to form organic matter, this costs energy; to provides it, the bacteria need oxygen. The reaction of hydrogen sulfide with oxygen releases the energy that powers the vent world (equivalent to the reaction of hydrogen with oxygen that powers ours) Only bacteria living right next to the vents, drawing from both worlds can pull off these reactions.
• The volcanism of our planet is largely driven by a continuous flow of seawater throughout the mantle. Its what keeps our world out of equilibrium. Its the turning of our world.
• All life on earth share common properties: composed of cells, have genes made of DNA, all encode proteins via a universal code of particular amino acids. All living things share a common energy currency ATP. All life shares common core of metabolic reactions known as the Krebs cycle. Normally this cycle consumes organic molecules (food) and pins off hydrogen (which will then be burned with oxygen) and carbon dioxide.
• Acids are defined in terms of protons: an acid is rich in protons and alkali (base) poor.
• The common ancestor of all life on earth was not a free-living cell but a rocky labyrinth of mineral calls, lined with catalytic walls composed of iron, sulfur and nickel and energized by proton gradients. The first life was a porous rock that generated complex molecules and energy right up to the formation of proteins and DNA itself. ( Life could not leave the vents until it had learned to harness its own chemiosmotic (the movement of protons over a membrane) gradient, but it could only harness its own gradient using genes and DNA. Life must have evolved a surprising degree of sophistication in its rocky hatchery.)
• There are 3e9 letters (base pairs) in the human genome. "3 gigabases" The human body has 15 million million cells ~ 1.5e13. Error rate of transcription of 1e-9.
• DNA morphs and twists, selection straightens
• Assuming that humans split off from chimps 6e6 years ago, and accumulated mutations at a rate of 200 per generation ever since, we would only have time to modify 1% of the genome.
• Deciphering the code of life was a larger achievement than in determining the double helix. The deciphered code was initially the most puzzling disappointment in modern biology, gives intriguing insights into how the DNA evolved in the first place.
• Genes code for proteins. DNA makes RNA, RNA makes proteins, Proteins are composed of a succession of building blocks called amino acids. Presumably, the sequence of letters in DNA encoded the sequence of amonio acids in proteins. Four different letters in DNA had to code for 20 amino acids. The actual code is degenerate, not an elegant solution! Three amino acids are coded by as many as six different codons, others by only one or two. This is the perfect antidote to the idea that beauty is any guide to truth in science. (Crick declared disappointing code as a "frozen accident") We have now come to realize that the code is neither frozen nor accidental. We now know that it is a "one in a million" able to resist change and speed up the pace of evolution at once. The real genetic code is startlingly resistant to change. B/c it looks designed, it must have evolved. But how can the code change without causing mayhem?
• There is a code within the codons which implies a physical process that could be stably optimized.
• the common ancestor of bacteria and archaea was not a free-living organism at all, but a replicator of sorts, confined to porous rock.
• Chlorophyll turns light from the sun into chemical energy.
• Without photosynthesis there would be no free oxygen. There might not be oceans, without oxygen there is not ozone which block UV rays. UV rays split water into oxygen and hydrogen. Hydrogen evaporates.

WhoWeAre

• Mars is dead. it is in near-perfect equilibrium.
• All animals and plants depend on oxygen. Life, in a world without free oxygen, is microscopic.
• All the oxygen put into the air by photosynthesis (co2-> c + o2) is taken out by respiration (o2 + c (food) -> co2). The only way that a planet can gain an oxygen atmosphere is if plant matter is preserved intact… it must be buried. Preserved plant matter is buried as coal, oil, natural gas, soot, charcoal in rocks deep in the earth. There is ~25k times more dead organic carbon trapped in the earth than living in the biosphere; the vast majority of organic carbon is buried as microscopic detritus in rocks like shales, inaccessible to human industry.
• There was an unprecedented rate of carbon burial in the Carboniferous era.
• From 2B to 1B years ago ("the boring billion") almost nothing of note happened.
• Oxygen liberated by photosynthesis comes from water, not co2. (This is the first step to solving the energy and climate crisis)
• Solar energy splits water into H and O2. Photosynthesis can do this (we haven't figured how to yet) with gentle sunlight rather than UV rays. We when figure out how to do it we will solve the worlds energy crisis; water is the most ubiquitous and raw material on our planet.

UnpopularImportantTruth

• Photosynthesis is conceptually simple: its all about electrons. Add a few electrons to CO2, along with a few protons to balance out charges and you get a sugar. Sugars are the ultimate source of all our food. Cyanobacteria split H2o to get the the electrons. Water is very stable: it has a high affinity for its electrons.
• Today the gap between plants and animals is perceived as narrow, while a huge gulf has opened up between bacteria and the rest of complex life. The crossing of this gulf causes much disagreement among scientists: How did life go from simplicity of bacteria to the complexity of plants and animals ? Was it always likely to happen? Would it happen elsewhere in the universe?
• On just one occasion a complex cell arose from bacteria, and went on to found all the great kingdoms of complex life: plants, animals, fungi and algae. And this progenitor cell, is very different from a bacterium. If we think of the tree of life, its as if bacteria make up the roots, while the familiar complex organisms make up branches. But whatever happened to the trunk?
• Everything that is anything on earth is eukaryotic. Eukaryotic cells have a true nucleus, distinguishing them from bacteria and is the key to understanding how they evolved from bacteria.
• For the first 3000 million years life (4000 to 1000 million years ago) bacteria dominated. They changed the world utterly, but barely changed themselves. The environmental changes brought about by bacteria were awesome, on a scale that humans can hardly conceive. All the oxygen in the air derives from photosynthesis. The "Great oxidation event" was when the air and oceans became flooded with oxygen around 2000 million years ago. Nothing is more conservative than bacterium.
• The Cambrian explosion is an archetypal eukaryotic affair - where large animals appeared in the fossil record for the first time.
• The transition from simple bacteria to complex eukaryotes was perhaps the single most important transition in the planets history.
• When Darwin was writing, there really was a missing link in the fossil record. This has now been filled in; any claims that there is still a missing link are untrue. It is the fine structure of genes, more than anything else, that has eliminated all the gaps.
• All life on the planet falls into three big groups (domains) Bacteria / Eukaryotes / Archaea
• Archaea were originally thought to be just a minor component of the Bacteria. Claim all the differences between plants an animals are small compared to that between Bacteria and Archaea. They amount to a missing link between bacteria and eukaryotes.
• The Eukaryotic cell did not evolve in s standard "Darwinian" way. but rather by some sort of big gene fusion: half archaea and half bacteria.
• mitochondria generate energy using oxygen.
• For biologists, respiration is the process in which food is reacted with oxygen to generate an internal voltage.
• The world is split into two. There are the eternal prokaryotes and the constantly changing eukaryotes. The transition from one to the other seems to have been a rapid accident between two prokaryotes cells, one getting inside the other. The new cell faced a host of problems, but one great freedom: the freedom to expand in size. Selfish genes posed one problem for which a happenstance solution was the nucleus and sex.
• Sex is a strange randominzer of genes. No sooner has sex engineered a winning combination that it dissolves them again.

WhoWeAre

• Most of us sense the magic of sex is the ability to pull a unique being from a hat every time. But its far from obvious that variety for variety's sake is a good thing. In fact, cloning gene combinations that have been found to be successful is often better.
• The list of the disadvantages should put off any sane person from sex for good: Sex can blight lives directly. Peacocks tail.

UnpopularImportantTruth

• Rooted to the spot, plants are the most implausible of sexual organisms, yet the overwhelming majority of them are.
• Flowering plants swept the world 80 million years ago. Flowers are pure cost to plants. They must attract pollinators with their colors and shapes; produce sweet nectar to make these visits worthwhile (nectar is a quarter sugar by weight); and distribute themselves with finesse – not too close (or inbreeding makes sex pointless) and not too far (or the pollinators will never make it to fertilize a partner). Having settled on a pollinator of choice, the flower and pollinator, evolve in tandem.
• No cost is more extreme than that paid by a tiny hummingbird for the static sex life of plants. The humming bird must be tiny, no larger bird could hover motionless over the flower. Its wings beating at 50 Hz, requiring a colossal metabolic rate. Hummingbirds need to refuel constantly. They extract more than half their own weight in nectar every day. If forced to stop feeding for more than a couple of hours, they fall unconscious. they have been seduced by they enchanged potions of plants into a life of bondage, moving relentlessly from flower to flower, distributing pollen, or collapsing in a coma.
• A race of cloning females ought to double in numbers every generation, a cloning female could swamp a population of a million sexually reproducing individuals in 50 generations. For sex to spread, sexual individuals would have to produce twice as many surviving offspring each generation. And yet the even-handed mechanics of sex are well understood: for every winner there is a loser. The explanation for the success of sex must be at once subtle and gigantic, staring us in the face, yet invisible.
• There must be big advantages for sex. The advantages are surprisingly hard to gauge and made the evolution of sex the "queen" of evolutionary problems though much of the 20 C.
• Sex juggles genes into new combinations, combinations that may never have existed before, which creates greater variation for natural selection to act on.
• Different mutations are most likely to occur in different individuals.
• The unrelenting competition between parasites and their hosts provides an endlessly shifting backdrop needed for sex to offer a big advantage.
• Rather than a gradual accrual of complexity of motion over time, it seems that there was a sudden shift after the great Permian extinction. At the heart of all this innovation is a single invention that made it all possible: muscle. Muscle is machines that convert chemical energy into mechanical force.
• The explosion of color in flowers and fruit was purely a response to the animal world.
• Muscle contraction depends on the properties of two molecules: actin and myosin. Both are composed of repeating protein units to form long filaments (polymers)
• The rate that myosin consumes ATP dictates the speed at which a muscle contracts.
• Sight is quite a rarity among life; the handful of phyla that did invent eyes utterly dominates animal life today. Many of the marvelous adaptations of life are a response to being seen. the invention of sight accelerated the pace and flow of evolution
• The Cambrian explosion happened when it did because a change in the environmental conditions permitted it. The evolution of large animals was most likely from the rising level of oxygen.
• Our thermostat is jammed at 37C 24 hours a day regardless of need. Hot blood exacts a cruel toll. It spells a short life, spent eating dangerously. It depresses the population size and number of offspring.
• A four chambered heart is significant because it splits the circulatory system in two. Half supplies the lungs, the other half the rest of the body; blood can be pumped at high pressure to the muscles, the brain and so on without damaging the delicate tissues of the lungs.
• We need to eat proteins to ensure that we get enough nitrogen in our diet, which is needed for making fresh proteins for ourselves, as well as DNA, both rich in nitrogen.
• We seem to view the world from a single cyclopean aperture in the front of the skull, which is quite obviously an illusion.

WhoWeAre

• Vision is more complex than it seems, but we can gain no sense of this complexity through introspection, and it could never have been predicted by a philosopher thinking about it logically.
• We perceive neither the brain nor the physical mind by thinking about it. Only the objective methods of science have linked the mind with the brain. Sensitive to so much of the world the brain has no pain preceptors of its own.
• Feelings feel real because they have real meaning, meaning that has been acquired in the crucible of selection, meaning that comes from real life, real death. Feeling are in reality a neural code, yet a code that is vibrant.

WhoWeAre

• Longer life is usually coupled with longer youth. Examples abound of animals whose life's have increased by a factor of 3 4 or 5X.
• Some animals (eg: freshwater Hydra) are essentially immortal - cells dies and are replaced, but the organism as a whole shows no signs of aging.
• Even if you are immortal, you are unlikely to live forever. Individuals who concentrate their reproductive resources in the earlier part of their life are statistically more likely to have more offspring.
• A gene that engenders even a tiny bit of sexual success is selected for even if it causes the most dreadful degeneration later on.
• All diseases of old age (from cancer to heart disease to Alzheimer's) can in principle be delayed, even avoided by simple permutations of a single pathway. Its a shocking conclusion, yet its staring us in the face. It should be easier to "cure" aging and all age-related diseases with a single panacea than it will ever be to cure any one age-related disease in people who are otherwise old. Age-related diseases depend on biological age, not chronological time. The significance of this cannot be overstated. Cure aging and we cure the diseases of old age – all of them. The overriding lesson from genetic studies is that aging is curable.

Longevity

• The most shocking fact in all of medicine: A tiny change in the mitochondria halves our risk of being hospitalized for any-related disease and double our prospects of living to 100. In principle, small adjustments to particular pathways should enable us to lead longer, healthier lives. Evolutionary theory suggests that we can eradicate the diseases of old age; the anti-aging pill is not a myth. If we spend a fraction of the time and effort dedicated to medical research on the underlying mechanisms of aging, I would be amazed if we didn't have an answer within the next two decades. And answer that cures all diseases of old age at once.

Longevity