The Human Body

The Body at a Glance

Stand up straight, face forward, arms by your sides with palms turned out, and you have adopted the anatomical position, the reference pose every anatomist uses. From it come the words that make sense of the map: anterior (front) and posterior (back), superior (towards the head) and inferior (towards the feet), medial (towards the midline) and lateral (away from it). An imaginary vertical slice through the nose and navel, the sagittal plane, divides the body into left and right halves that look like mirror images. "Left" always means the body's own left, which is why a drawing of someone facing you shows their heart on your right.

Outside, the symmetry is convincing. Inside, it is not. The liver, the largest internal organ at about 1.5 kilograms, sits mostly on the right beneath the ribs; the stomach and spleen lie to the left; the left lung has two lobes to the right lung's three, leaving a notch for the heart. Roughly one person in 10,000 has situs inversus, a complete mirror-image arrangement of the organs, and may find out only from a scan.

The organs are packed into protected compartments called body cavities. The skull holds the brain, around 1.3 to 1.4 kilograms of tissue that uses about a fifth of the body's resting energy. The thoracic cavity, caged by 24 ribs, holds the heart and lungs. A dome of muscle, the diaphragm, separates it from the abdominal cavity below, home to the stomach, liver, intestines and kidneys, which runs on into the pelvic cavity with the bladder and reproductive organs.

Did you know? The heart sits almost in the middle of the chest, behind the breastbone; only its lower tip angles to the left, which is where you feel the beat.

The overall inventory is impressive: 206 bones in a typical adult, more than 600 skeletal muscles, around five litres of blood, and a skin covering roughly 1.5 to 2 square metres. About 60 per cent of an adult man's weight is water, a little less in women, who on average carry more fat.

Much of this map was drawn surprisingly late. For some 1,300 years European medicine followed the Greek-born Roman physician Galen, who had dissected mostly animals such as pigs and monkeys. In 1543 Andreas Vesalius published De humani corporis fabrica, based on human dissection, and corrected many of Galen's errors, from the lobes of the liver to the lower jaw, which in humans is a single bone. The map still matters every day: surgeons rely on surface landmarks, and the pain of appendicitis typically begins near the navel before settling low on the right. The body is a well-organised building, and knowing where the rooms are is the first step to understanding how it runs.

Thirty-Seven Trillion Cells

Counting the cells in a human body sounds like a job nobody could do, and in a literal sense nobody has. Instead, scientists estimate organ by organ, multiplying the volume of each tissue by the typical size or density of its cells. In 2013 a team led by Eva Bianconi arrived at about 37 trillion for an average adult. A 2016 revision by Ron Sender, Shai Fuchs and Ron Milo, working from a 70-kilogram reference man, suggested around 30 trillion. Either way, it is several thousand times the number of people on Earth.

The surprise is how unevenly those cells are shared out. About five in every six are red blood cells, tiny discs only 7 to 8 micrometres across (a micrometre is a thousandth of a millimetre). They are so small and so numerous that they dominate the count while making up only a few per cent of body mass. Next come platelets, the cell fragments that plug leaks, at around 1.5 trillion. The brain's 86 billion neurons, for all their importance, are a rounding error in the census. By weight the story flips: muscle cells and fat cells, few but large, account for most of the body's cellular mass.

Sizes vary enormously. The human egg, about 0.1 millimetres wide, is the largest cell and just visible to the naked eye; a sperm head is around 5 micrometres long. A motor neuron that moves the big toe has its cell body in the lower spinal cord and a single fibre, an axon, that can reach about a metre in a tall adult.

Did you know? Your body carries roughly as many bacteria as human cells, about 38 trillion, mostly in the colon; the old claim that microbes outnumber us ten to one rested on a rough estimate from the 1970s.

Cells are also constantly replaced. Recent estimates suggest that about 330 billion cells are renewed every day, around 1 per cent of the total, the great majority of them blood cells and the lining of the gut. A red cell lasts about 120 days, while cells on the surface of the small intestine last only a few days. Others stay for life, including most neurons of the brain's cortex and the fibre cells at the core of the eye's lens.

The idea that living things are made of cells is younger than the telescope. Robert Hooke coined the word cell in 1665, after seeing the box-like compartments of cork under his microscope. In 1838 and 1839 Matthias Schleiden and Theodor Schwann proposed that all plants and animals are built of cells, and Rudolf Virchow later popularised the principle that every cell comes from another cell. When that orderly division breaks down and cells multiply without restraint, the result is cancer. Meanwhile, a single pinprick of blood, one microlitre, holds around five million red cells: the population of a small country in a dot you could wipe away with a fingertip.

Inside a Cell

A typical human cell is around 10 to 30 micrometres across, so a couple of dozen could sit side by side across the full stop at the end of this sentence. Inside, it is less a bag of jelly than a busy factory. Its outer wall is the cell membrane, a double layer of fatty molecules called phospholipids, only about 7 to 10 nanometres thick and studded with proteins that act as gates, pumps and receivers. Everything inside it apart from the nucleus is the cytoplasm, a crowded watery gel in which the working parts, the organelles, are suspended.

The nucleus is head office. It keeps the DNA behind a double membrane pierced by thousands of pores, and it contains a dense spot, the nucleolus, where the parts of ribosomes are assembled. Instructions leave the nucleus as messenger molecules; the DNA itself stays at home.

Manufacturing happens on ribosomes, molecular machines that build proteins. Many sit on the rough endoplasmic reticulum, a folded maze of membranes where new proteins are threaded in and folded. Small bubbles called vesicles carry them on to the Golgi apparatus, a stack of flattened sacs that trims, labels and sorts them for use inside the cell or export outside it. Waste goes to lysosomes, sacs of digestive enzymes working at an acidity of around pH 5, which break down worn-out parts and captured invaders. All of it is held in shape by the cytoskeleton, a scaffold of protein filaments that also serves as tracks along which motor proteins haul their cargo.

Power comes from mitochondria, bean-shaped organelles that combine oxygen with fuel from food to make ATP, the cell's energy currency. A liver cell may contain a thousand or more. Mitochondria have their own small loop of DNA, carrying 37 genes and inherited almost entirely from the mother. That is a clue to their origin: they are thought to descend from bacteria engulfed by an ancestral cell well over a billion years ago, an idea championed by Lynn Margulis from 1967.

Did you know? Mature red blood cells eject their nucleus and have no mitochondria, so they use none of the oxygen they carry.

Most of this was invisible until the electron microscope. Camillo Golgi saw his apparatus in 1898 with a silver stain, but some doubted it was real until electron images settled the matter in the 1950s. Albert Claude, Christian de Duve and George Palade, who between them mapped the cell's secretory pathway and discovered lysosomes, shared a Nobel Prize in 1974. When one part fails, the effects are precise: in Tay–Sachs disease a missing lysosomal enzyme lets a fatty substance build up in nerve cells. On a happier note, endurance training prompts muscle cells to build more mitochondria, one reason fitness improves with practice. Every one of your cells is a factory that never closes.

DNA: The Instruction Manual

Almost every cell in your body carries a complete copy of the instructions for building you. They are written in DNA, deoxyribonucleic acid, a long molecule shaped like a twisted ladder: the double helix. Each side rail is a chain of sugar and phosphate, and each rung is a pair of chemical letters called bases. There are four, adenine, thymine, cytosine and guanine, and they pair by strict rule, A with T and C with G. Because each strand dictates the other, the molecule carries a built-in template for copying itself.

A full set of human instructions, the genome, runs to about 3.1 billion base pairs, and most cells carry two sets, one from each parent, divided among 46 chromosomes in 23 pairs. Stretched out, the DNA in a single cell would be about 2 metres long, yet it fits inside a nucleus roughly 6 micrometres wide. It manages this by winding around spools of proteins called histones, forming nucleosomes like beads on a string, which then fold and loop into dense chromatin. The helix itself is only about 2 nanometres wide.

A gene is a stretch of DNA that carries the recipe for a protein or a working RNA molecule. Humans have roughly 20,000 protein-coding genes, far fewer than many scientists expected and about as many as a tiny roundworm. The protein-coding parts make up only 1 to 2 per cent of the genome; much of the rest helps decide when and where genes are switched on, and some has no known function.

Did you know? Any two people share about 99.9 per cent of their DNA sequence, yet the remaining 0.1 per cent still amounts to millions of letters.

The road to the helix was long. Friedrich Miescher isolated a substance he called "nuclein" from pus-soaked bandages in 1869. In 1952 Rosalind Franklin and her student Raymond Gosling recorded an X-ray image, Photograph 51, that revealed a helical pattern. Drawing on her data among other clues, James Watson and Francis Crick published their double-helix model in 1953, noting with famous understatement that the pairing "immediately suggests a possible copying mechanism for the genetic material". The Human Genome Project declared its sequence essentially complete in 2003, and the last stubborn gaps were closed in 2022.

Every time a cell divides it copies all six billion or so letters, and proofreading enzymes keep mistakes to roughly one in a billion. A single wrong letter can still matter: sickle cell disease results from one change in the gene for a part of haemoglobin, which makes red cells stiffen and buckle. Most changes, though, are harmless, and they are the raw material of individuality. That near-perfect copying is why a child can inherit a grandmother's chin: the manual is passed on, page by page, with remarkably few typos.

Proteins: The Body's Workers

If DNA is the instruction manual, proteins are the workforce. They carry oxygen, digest food, contract muscles, build hair, copy DNA, fight infection and relay messages between cells. Apart from water, protein is the largest part of a cell's mass, and the body makes many thousands of different kinds.

Every protein is a chain of building blocks called amino acids, of which the body uses 20. Making one takes two stages. First, in the nucleus, an enzyme called RNA polymerase copies a gene into a mobile working copy, messenger RNA; this is transcription. The messenger slips out through a nuclear pore into the cytoplasm, where a ribosome clamps onto it and reads it three letters at a time. Each triplet, or codon, specifies one amino acid, delivered by a matching adaptor molecule called transfer RNA. The ribosome links the amino acids one by one, at a few per second in human cells, until it meets a stop codon. This is translation. With four letters read in threes there are 64 codons, more than enough for 20 amino acids plus start and stop signals.

A chain is not yet a working protein. It must fold, usually in well under a second, into a precise three-dimensional shape. Stretches coil into spirals called alpha helices or pleat into flat beta sheets, and the whole thing packs into a compact form. Some proteins then team up. Haemoglobin, which carries oxygen in red cells, is four chains totalling 574 amino acids, each cradling an iron-containing haem group. Shape is function: an enzyme's pocket fits its target the way a lock fits a key.

Did you know? The largest known human protein, titin, a molecular spring in muscle, can be more than 34,000 amino acids long.

Proteins vary hugely in size and role. Insulin is a mere 51 amino acids; Frederick Sanger had worked out its full sequence by 1955, the first protein ever sequenced, and won a Nobel Prize in 1958. The first three-dimensional structures, of myoglobin and haemoglobin, were solved by X-ray crystallography by John Kendrew and Max Perutz between 1958 and 1960. The most abundant protein in the body is collagen, the rope-like fibre of skin, tendon and bone, which makes up roughly a quarter to a third of all protein.

When folding goes wrong, the results can be serious. In cystic fibrosis, the commonest faulty version of a channel protein misfolds and is destroyed before it can reach the cell surface. In prion diseases, a misfolded protein forces normal copies of itself to misfold too. You can watch proteins change shape in your own kitchen: heat unfolds the proteins in egg white, turning a clear runny liquid into a firm white solid, and no amount of cooling will turn it back. A gene is only a recipe; the protein is the dish, and its shape is everything.

Stem Cells

Every one of your 200 or so specialised cell types, from neurons to fat cells, descends from a single cell: the fertilised egg. A stem cell is any cell that keeps something of that original promise. It has two defining talents. It can self-renew, dividing to make more stem cells, and it can differentiate, giving rise to cells that specialise.

Stem cells come in grades of versatility, known as potency. The fertilised egg and its first few daughter cells are totipotent: they can form a whole body plus the placenta. By about five days after fertilisation the embryo is a hollow ball of a hundred or more cells, the blastocyst, with a cluster inside called the inner cell mass. These cells are pluripotent: they can become any cell type in the body. As the embryo develops they sort into three germ layers. The ectoderm gives rise to skin and the nervous system; the mesoderm to muscle, bone, blood and heart; the endoderm to the lining of the gut and lungs and to organs such as the liver.

Adults keep smaller reserves of multipotent adult stem cells, each limited to its own tissue. The busiest live in the bone marrow, where haematopoietic stem cells (blood-forming cells) and their descendants turn out around two million red cells every second, as well as white cells and platelets. Stem cells in the deep folds of the gut lining replace its surface every few days, and those at the base of the skin's outer layer renew it roughly every month. Other tissues are far thriftier: heart muscle cells are replaced at only about 1 per cent a year in young adults, and more slowly with age.

Did you know? That heart estimate came from carbon-14 released by Cold War nuclear tests, which left a datable stamp in the DNA of every cell made since.

The existence of blood stem cells was shown in 1961 by James Till and Ernest McCulloch in Toronto, who noticed lumps on the spleens of irradiated mice, each a colony grown from a single marrow cell. Bone marrow transplantation, pioneered by E. Donnall Thomas, remains the most established stem cell therapy. In 2006 Shinya Yamanaka showed that switching on just four genes could turn adult mouse cells back into pluripotent ones, now called induced pluripotent stem cells. He shared the 2012 Nobel Prize with John Gurdon, who had reprogrammed frog cells decades earlier.

When blood-forming cells acquire harmful mutations, they can give rise to leukaemia. Many proposed stem cell treatments beyond blood and marrow transplants remain experimental and are still being tested in regulated trials. Yet the everyday work of stem cells never stops: after a blood donation, the marrow quietly replaces the lost red cells within about four to six weeks. You are, in a very real sense, being rebuilt from within all the time.

Four Kinds of Tissue

Look closely at any organ and you find the same four materials, mixed in different proportions. A tissue is a group of similar cells, together with the material between them, working at one job. The French anatomist Xavier Bichat, working in the 1790s largely without a microscope, teased organs apart by boiling, drying and soaking them, and identified 21 kinds of tissue; the word comes from the French tissu, a woven fabric. Microscopes later reduced his list to four.

Epithelial tissue covers and lines. It forms the outer layer of the skin, the lining of the gut and airways, and the walls of glands. Its cells are packed tightly in sheets, anchored to a thin mat called the basement membrane, with no blood vessels of their own; they are fed by diffusion from below. Their shapes reveal their jobs: flat squamous cells for thin barriers such as the air sacs of the lungs, cube-shaped cells in kidney tubules, tall columnar cells in the gut. Because it faces constant wear, epithelium renews quickly, and the skin's outer layer turns over in about a month.

Connective tissue holds the body together and is defined less by its cells than by what lies between them, the extracellular matrix. Change the matrix and you change the tissue: tough collagen fibres make tendons, a rubbery gel makes cartilage, mineral crystals make bone, and a liquid matrix makes blood. Fat is connective tissue too.

Muscle tissue contracts. Skeletal muscle, striped under the microscope, moves the bones under voluntary control. Cardiac muscle, also striped, is found only in the heart and beats without any conscious command. Smooth muscle, without stripes, squeezes the gut, the bladder and the walls of blood vessels. Nervous tissue carries signals: neurons send electrical impulses, at up to about 120 metres per second in the fastest fibres, while glial cells feed, insulate and protect them.

Did you know? Blood counts as a connective tissue: its cells float in a liquid matrix, the plasma, which makes up a little over half its volume.

The four families also explain much about disease. Around 80 to 90 per cent of cancers arise in epithelium, the tissue that divides most busily, and are called carcinomas; the much rarer cancers of connective tissue are sarcomas. Everyday injuries reveal the layers too. A blister is fluid pooling within the epithelium of the skin; a graze that bleeds has broken through into the connective tissue beneath, where the blood vessels run; and a paper cut stings because it reaches the nerve endings. Arrange the same four fabrics in different ways and you get a lip, a tendon or a liver.

Organs and Systems

The body is organised like a set of nesting boxes. Atoms join into molecules, molecules build cells, similar cells form tissues, tissues combine into organs, and organs cooperate in organ systems. An organ is a distinct structure made of at least two kinds of tissue that does a particular job. The stomach is a good example: epithelium lines it and secretes acid, smooth muscle churns its contents, connective tissue binds the layers and carries the blood vessels, and nerves coordinate the whole.

Anatomists usually group the organs into 11 systems. The integumentary system (skin, hair and nails) is the outer barrier. The skeletal and muscular systems give shape and movement. The nervous and endocrine systems are the two control networks, one fast and electrical, the other slower and chemical. The cardiovascular system pumps blood; the lymphatic and immune system drains fluid and fights infection; the respiratory system exchanges gases; the digestive system breaks down food; the urinary system filters the blood and removes waste; and the reproductive system makes the next generation.

How many organs there are depends on who is counting. A commonly quoted figure is 78, but lists vary widely depending on whether each bone, gland or muscle counts separately. Even the definition moves: in 2016 the surgeon J. Calvin Coffey and colleagues argued that the mesentery, the fold of tissue that anchors the intestines, is a single continuous organ, a view now widely accepted. The largest organ of all is the skin; the largest internal one is the liver.

Did you know? People can live without a surprising number of organs, including the spleen, the gallbladder, the appendix, one kidney, one lung and large parts of the liver and intestines.

Systems rarely work alone. Run for a bus and your nervous system fires the muscles, which pull on the skeleton; the endocrine system releases adrenaline; heart and lungs speed up to deliver oxygen; and the skin sweats to shed the extra heat. Some organs even hold two memberships: the pancreas belongs to both the digestive and the endocrine systems.

This interdependence explains why failure in one place spreads. Kidney failure disturbs blood pressure and the balance of salts; a failing heart leaves fluid pooling in the lungs and legs. It also explains why replacing an organ once seemed unthinkable. In 1954 in Boston the surgeon Joseph Murray transplanted a kidney from Ronald Herrick into his identical twin, Richard, who lived for another eight years; Murray later shared a Nobel Prize. Today kidneys, livers, hearts and lungs are transplanted routinely around the world. The lesson of the body plan is simple: no organ is an island.

What We Are Made Of

Strip a human body down to its elements and the list is short. By mass, about 65 per cent is oxygen, 18 per cent carbon, 10 per cent hydrogen and 3 per cent nitrogen. Add calcium, at about 1.5 per cent, and phosphorus, at about 1 per cent, and those six elements account for roughly 99 per cent of you. Potassium, sulfur, sodium, chlorine and magnesium make up most of the rest, well under 1 per cent between them.

Oxygen tops the list largely because of water. About 60 per cent of an adult's weight is water, around 42 litres in a 70-kilogram man, and a water molecule is almost nine-tenths oxygen by weight. Count atoms instead of weighing them and the order changes: hydrogen, the lightest element, makes up about 62 per cent of all the atoms in your body, oxygen about 24 per cent and carbon about 12 per cent. A 70-kilogram person contains roughly 7 billion billion billion atoms.

Carbon is the structural star. Each carbon atom can bond to four others at once, forming the long chains and rings of proteins, fats, sugars and DNA. Grouped by molecule, a typical adult is about 60 per cent water, 15 to 17 per cent protein, a widely variable share of fat, around 6 per cent minerals, mostly in bone, and only about 1 per cent carbohydrate, stored as glycogen in the liver and muscles.

Did you know? When you lose fat, most of it leaves your body as carbon dioxide that you breathe out; a 2014 calculation found the lungs carry away about 84 per cent of it.

Some elements matter far beyond their weight. An adult holds only about 4 grams of iron, most of it in haemoglobin, where it binds oxygen; too little causes anaemia. The thyroid needs iodine, about 15 to 20 milligrams in the whole body, to make its hormones, and without enough the gland may swell into a goitre. Zinc, copper, selenium and a handful of others are needed in trace amounts, often as working parts of enzymes.

The French chemist Antoine Lavoisier was among the first to see the body in these terms. In the early 1780s, working with Pierre-Simon Laplace, he measured the heat given off by a guinea pig inside an ice calorimeter and concluded that breathing is a slow form of combustion, burning carbon with oxygen. Almost every atom in that chemistry has a cosmic past. The hydrogen dates from the Big Bang; the carbon, oxygen, calcium and iron were forged inside stars and scattered when they died. As Carl Sagan put it, "We are made of star-stuff." Every breath and every meal is a trade in the oldest materials in the universe.

Homeostasis: Keeping in Balance

Outside, the weather can swing from frost to heatwave; inside, your core temperature stays within about a degree of 37 °C. This steadiness is homeostasis, the body's ability to keep its internal conditions within narrow limits whatever happens around it. Temperature is the most familiar example, but the same holds for blood sugar, which normally sits around 4 to 6 millimoles per litre between meals, for the acidity of the blood, held between pH 7.35 and 7.45, and for water, salt, oxygen and carbon dioxide.

Most of this control works by negative feedback, the principle of a household thermostat. Every loop has three parts. Sensors detect a change: nerve endings in the skin and temperature-sensitive cells in the brain keep watch on heat. A control centre compares the reading with a set point; for temperature this is the hypothalamus, a region about the size of an almond at the base of the brain. Effectors then act to reverse the change, and as conditions return to normal the response winds down.

When you overheat, the hypothalamus tells blood vessels in the skin to widen, so warm blood can lose heat at the surface, which is why a hot face flushes. It also switches on the sweat glands; evaporating sweat carries heat away, and in hot conditions a person can sweat more than a litre an hour. When you are cold, skin vessels narrow, keeping warm blood in the core and leaving fingers pale, and muscles begin to shiver, generating heat through rapid small contractions. Tiny muscles at the base of each hair contract too, raising goosebumps, a leftover from furrier ancestors in whom raised hair trapped an insulating layer of air.

Did you know? The famous 37 °C comes from Carl Wunderlich, who in 1868 published averages from around a million armpit readings; modern measurements put the typical figure slightly lower, at roughly 36.6 to 36.8 °C.

The idea has French roots. From the 1850s the physiologist Claude Bernard argued that a stable milieu intérieur, the internal environment, is the condition for a free and independent life. In 1926 the American physiologist Walter Cannon coined the word "homeostasis", and he explored it in his book The Wisdom of the Body in 1932. Not every loop is negative. In childbirth, contractions trigger the release of the hormone oxytocin, which strengthens the contractions in turn, a positive feedback loop that runs until the baby is born.

When homeostasis is overwhelmed, the consequences can be grave. A core temperature above about 40 °C can bring heatstroke, and one below 35 °C counts as hypothermia. Diabetes is, at heart, a failure of blood sugar control. So the next time you shiver at a bus stop, remember that it is not weakness but a thermostat at work, keeping you alive by a matter of degrees.

The Skeleton

Strip away everything soft and an adult is held up by about 206 bones, a frame weighing roughly 15 per cent of the body. It is really two skeletons in one. The axial skeleton, the central column of skull, spine, ribs and breastbone, has 80 bones and guards the brain, spinal cord, heart and lungs. The appendicular skeleton, 126 bones in the limbs and the girdles that hang them from the trunk, does most of the moving. Remarkably, more than half of all our bones, 106 of them, sit in the hands and feet.

A skeleton works as a system of levers. Bones are rigid bars, joints are pivots, and muscles, anchored by tendons, pull across them. The femur, or thigh bone, is the longest and strongest, roughly a quarter of a person's height; the stapes in the middle ear, at about 3 millimetres, is the smallest. The clavicle, or collarbone, props the shoulder away from the chest like a strut, which is why it is among the most commonly broken bones when people fall on an outstretched hand.

The frame is also a store and a factory. About 99 per cent of the body's calcium is locked in bone and released when the blood runs short, and red marrow in the hips, ribs, breastbone and vertebrae makes blood cells. Nor is the number of bones fixed. A newborn has nearer 300 bony pieces, many still partly cartilage, and they fuse through childhood; the last growth plates close in the early twenties. The skull and the sacrum, at the base of the spine, are the clearest examples of many pieces merging into one.

Did you know? The hyoid, a small U-shaped bone in the neck that anchors the tongue, is the only bone in the body that does not form a joint with any other bone.

For some 1,300 years European anatomy followed Galen, a Greek physician in Rome whose descriptions were based largely on dissected apes and other animals. In 1543 Andreas Vesalius, teaching in Padua, published De humani corporis fabrica, illustrated with superb woodcuts drawn from human dissection. It corrected scores of errors, including Galen's claim that the human lower jaw is made of two bones.

Because bone is living tissue, it responds to how it is used. Walking, running and lifting keep it dense; long bed rest or spaceflight thins it. In osteoporosis, common in older age and especially in women after the menopause, bone is lost faster than it is rebuilt, so a wrist, hip or vertebra can break after a minor fall. The skeleton in a museum case looks dry and finished. The one inside you is quietly rebuilding itself, piece by piece, for life.

Inside a Bone

Cut a long bone such as the femur across its middle and it looks less like a solid rod than a pipe. A tough skin, the periosteum, wraps the outside and is rich in nerves and blood vessels, which is why a knock on the shin hurts so much. Beneath it lies a dense wall of compact bone, several millimetres thick, and inside that a central medullary cavity filled, in adults, with fatty yellow marrow. Towards each end the wall thins and the interior fills with spongy bone, a honeycomb of tiny struts called trabeculae.

Bone is a composite, rather like reinforced concrete. Roughly two-thirds of its weight is mineral, crystals of calcium phosphate called hydroxyapatite, which resist squashing. Most of the remaining third is collagen, a fibrous protein that resists bending and snapping. Soak a chicken bone in vinegar for a few days to dissolve the mineral and it bends like rubber; bake it hard enough to destroy the collagen and it crumbles.

Compact bone is built from millions of osteons, tiny cylinders about 0.2 millimetres across, each made of concentric rings of bone around a central canal that carries blood vessels and nerves. The English physician Clopton Havers described these canals in 1691, and they still bear his name. Trapped in little chambers between the rings are osteocytes, mature bone cells that reach out to one another through hair-thin channels and sense strain. Compact bone makes up about 80 per cent of the skeleton's mass. Spongy bone, light but braced along the lines of stress, makes up the rest.

Bone is never finished. Two teams of cells work on it constantly. Osteoclasts, large cells with many nuclei, dissolve old bone with acid and enzymes; osteoblasts follow behind, laying down fresh collagen that then mineralises. Through this remodelling an adult replaces roughly a tenth of the skeleton each year. In 1892 the German surgeon Julius Wolff argued that bone adapts to the loads placed on it, an idea now called Wolff's law. The racket arm of a professional tennis player has measurably thicker bone than the other arm.

Did you know? Red marrow, found mainly in the flat bones and the ends of long bones in adults, produces around two million new red blood cells every second.

When the balance tips, trouble follows. Astronauts in weightlessness can lose roughly 1 per cent of the bone in their hips each month, and osteoporosis is a slow version of the same imbalance on Earth. A broken bone, by contrast, shows the system at its best: a blood clot forms, a soft callus of cartilage bridges the gap, hard bone replaces it and remodelling smooths the join over months. Few materials made by engineers can repair themselves at all. Bone does it as routine.

The Skull

The skull is a helmet, a face and a set of jaws fused into one. Usually counted as 22 bones, it divides into the cranium, eight bones forming a vault around the brain, and fourteen facial bones that frame the eyes, nose and mouth. The vault is made of the frontal bone at the forehead, two parietal bones forming the roof and sides, two temporal bones at the temples, the occipital bone at the back, and two less visible bones, the sphenoid and ethmoid, in its floor. Only one bone moves freely: the mandible, or lower jaw.

The cranial bones meet at wavy seams called sutures, joints of tough fibrous tissue that interlock like jigsaw pieces. At birth they are still loose, and the gaps where several bones meet are covered by membrane: the fontanelles, or soft spots. This flexibility lets the skull mould slightly as a baby passes through the birth canal, and leaves room for a brain that more than doubles in size in the first year. The large front fontanelle usually closes by about 18 months to two years.

The adult cranium encloses about 1,300 cubic centimetres, room for a brain of around 1.3 to 1.4 kilograms cushioned in fluid. At the base, a large opening called the foramen magnum lets the spinal cord pass down into the spine, and dozens of smaller holes carry nerves and blood vessels in and out. Air-filled spaces, the sinuses, lighten the facial bones and add resonance to the voice. The jaw hinges and slides at the temporomandibular joint just in front of each ear: put your fingertips there and open your mouth to feel it glide forward. Driven by the masseter, one of the strongest muscles for its size, the back teeth can bite with a force of several hundred newtons.

Did you know? The temporal bone, which houses the delicate organs of hearing and balance, contains the densest bone in the body, its petrous part, a name that simply means stony.

In the early 1800s the German physician Franz Joseph Gall popularised phrenology, the claim that bumps on the skull revealed character and talents. It was wrong: the outer shape of the skull says almost nothing about the brain beneath, and experiments had discredited the idea among scientists by the middle of the century. Yet Gall's hunch that different parts of the brain do different jobs turned out to be roughly right, a good idea arriving inside a bad one.

Skull injuries matter mainly for what lies inside. A blow can bruise the brain or cause bleeding even without a fracture, which is why helmets are designed to spread and slow an impact. In craniosynostosis, one or more sutures fuse too early in infancy and distort the growing head, and surgeons can release them. In daily life the skull reveals itself in smaller ways: the click of a jaw, the pressure of a blocked sinus during a cold. Thin, light and immensely strong, it is the body's best-defended room.

The Spine

The spine, or vertebral column, begins as a stack of 33 vertebrae. Seven cervical vertebrae form the neck, twelve thoracic vertebrae carry the ribs, and five large lumbar vertebrae bear the weight of the lower back. Below them five vertebrae fuse into the sacrum, wedged between the hip bones, and three to five tiny ones fuse into the coccyx, or tailbone. That leaves 24 movable vertebrae in an adult, in a column about 70 centimetres long.

Each vertebra has two main parts. In front is the vertebral body, a short cylinder of spongy bone that carries the load; the bodies grow larger down the column, because each bears more weight than the one above. Behind it the vertebral arch encloses a ring, and stacked together the rings form the spinal canal that shelters the spinal cord. Bony projections stick out to the sides and back as anchors for muscles. The knobbly ridge you can feel down the middle of your back is the row of spinous processes. Between the bodies sit 23 intervertebral discs, each a tough fibrous outer ring, the annulus fibrosus, around a jelly-like core, the nucleus pulposus.

Seen from the side, a healthy spine is not straight but a gentle double S. The neck and lower back curve forwards; the chest and sacral regions curve backwards. A newborn's spine is a single C. The neck curve develops as a baby learns to hold up its head, and the lower-back curve as it learns to stand and walk. The curves act like a spring, absorbing shocks and balancing the head over the hips with little muscular effort. At the top, the first two vertebrae are specialised: the atlas lets you nod, and the axis, with a peg on which the atlas pivots, lets you shake your head.

Discs are mostly water, and they behave like sponges. Under the load of a day spent upright they slowly squeeze out fluid, so most people are around a centimetre shorter at bedtime than when they woke, regaining it overnight. Astronauts, freed from gravity, can grow by up to about 5 centimetres in orbit, often with back pain as a side effect.

Did you know? A giraffe has the same number of neck vertebrae as you: seven. Almost all mammals do; theirs are simply much longer.

The spinal cord is shorter than the column, ending near the first or second lumbar vertebra, with a bundle of nerve roots continuing below. That is why a needle can be placed in the lower back to sample spinal fluid, a procedure introduced by the German physician Heinrich Quincke in 1891. When things go wrong, the causes are usually mechanical. A disc's outer ring can tear, letting the core bulge out and press on a nerve root: a herniated disc, which can send pain down the leg. Scoliosis is a sideways curve, often appearing in adolescence, and low back pain is one of the commonest complaints of adult life. Flexible, load-bearing and protective at once, the spine is a compromise that mostly works.

Joints

Wherever two bones meet there is a joint, and the adult body has somewhere between 250 and 350 of them, depending on how they are counted. Anatomists sort them by what holds the bones together. Fibrous joints, such as the sutures of the skull, are bound by dense tissue and barely move. Cartilaginous joints, such as the discs between vertebrae and the pubic symphysis at the front of the pelvis, allow a little give. The joints we usually think of, the knees, hips and knuckles, are synovial joints, built for movement.

A synovial joint is a sealed capsule. The ends of the bones are capped with smooth, glassy articular cartilage, a few millimetres thick at the knee. A fibrous joint capsule surrounds them, lined by the synovial membrane, which secretes synovial fluid, a slippery liquid with the consistency of raw egg white. With every movement the cartilage squeezes fluid in and out like a sponge, which both lubricates the joint and nourishes the cartilage, since it has no blood supply of its own. The result is friction lower than ice sliding on ice.

Synovial joints come in six shapes, each allowing different movements. Ball-and-socket joints at the hip and shoulder swing in every direction and rotate. Hinge joints at the elbow and between the finger bones bend in one plane, like a door. A pivot joint lets the radius roll around the ulna as you turn a key, and lets the head turn on the neck. The saddle joint at the base of the thumb rocks in two directions, the condyloid joint at the wrist allows nodding and side-to-side movement, and plane joints between the small bones of the wrist and ankle simply glide. The shoulder trades stability for range: it is the most mobile joint in the body and the one most often dislocated.

Cracking your knuckles is a joint event too. Pulling the bones apart drops the pressure in the synovial fluid until a gas-filled cavity suddenly forms, a moment caught on MRI film in 2015, and the same knuckle cannot crack again for around 20 minutes. The American doctor Donald Unger cracked the knuckles of his left hand but not his right for about 60 years and found no arthritis in either, a one-man experiment that won him an Ig Nobel Prize in 2009.

Did you know? Climbing stairs loads each knee with roughly three to four times your body weight.

Because cartilage has no blood vessels, it heals poorly. In osteoarthritis, the commonest joint disease, the cartilage wears and frays over years, the bone beneath thickens and spurs form, and the joint grows stiff and sore. In rheumatoid arthritis the immune system attacks the synovial membrane itself. Worn hips and knees are now routinely replaced with metal, ceramic and plastic implants, one of surgery's great successes. Most of the time, though, joints work so smoothly that we notice them only when they creak.

The Hand

Each hand holds 27 bones: eight small carpals in the wrist, arranged in two rows of four, five metacarpals in the palm and fourteen phalanges in the fingers, three in each finger and two in the thumb. Together the two hands account for more than a quarter of the body's bones. They are linked by dozens of joints and bound by a dense web of ligaments, yet each finger can bend, straighten, spread and close on command.

Surprisingly, the fingers contain no muscles at all. The powerful muscles that curl and straighten them sit in the forearm and pull on long tendons that run through the wrist like the strings of a puppet; clench a fist and watch your forearm tighten. On the palm side, nine tendons and the median nerve squeeze through the carpal tunnel, a narrow channel formed by the carpal bones and a tough ligament across them. Swelling there compresses the nerve and causes carpal tunnel syndrome, with tingling in the thumb and first fingers. Small muscles inside the palm, the intrinsic muscles, handle fine adjustments such as spreading the fingers.

The key to the hand is the thumb. Its metacarpal meets a wrist bone, the trapezium, at a saddle joint, shaped like two saddles set crosswise, which lets the thumb swing across the palm to meet each fingertip. This opposition makes two kinds of grip possible, as the British anatomist John Napier described in 1956. In the power grip the fingers wrap an object against the palm, as when holding a hammer; in the precision grip thumb and fingertips pinch, as when threading a needle. Chimpanzees have opposable thumbs too, but theirs are short compared with their long fingers, so their precision grip is less refined.

Running a hand takes a lot of brain. From the 1930s the Canadian neurosurgeon Wilder Penfield, gently stimulating the exposed brains of conscious patients during surgery, mapped which areas moved which parts of the body. The hand and fingers claimed a strikingly large strip of the motor cortex, far more than the back or thigh. Some fingers, however, are not fully independent. Fold your middle finger down onto the palm and try to lift your ring finger: it barely moves, because the two share a muscle and their extensor tendons are tied together by bands of tissue.

Did you know? Fingerprints form in the womb between about the tenth and sixteenth weeks of pregnancy, and even identical twins have different ones.

Hands are also easily hurt. A fall on an outstretched hand commonly breaks the end of the radius at the wrist, or the scaphoid, a carpal bone with a poor blood supply that can be slow to heal. Arthritis often appears first at the base of the thumb and in the finger joints. Each time you button a shirt or type a message, a forearm, a wrist and a skein of tendons perform a feat no robot hand has quite matched.

Feet and Walking Upright

Each foot has 26 bones, 33 joints and more than 100 muscles, tendons and ligaments. Seven tarsals make up the ankle and heel, including the talus, which forms the ankle joint with the bones of the shin, and the calcaneus, the heel bone. Five metatarsals span the middle of the foot, and fourteen phalanges form the toes. Unlike an ape's foot, ours has a big toe lined up with the others: we gave up gripping branches in exchange for pushing off the ground.

The bones are arranged in three arches: a high inner arch along the instep, a lower outer arch, and a transverse arch across the ball of the foot. Ligaments and a thick sheet of tissue on the sole, the plantar fascia, tie the arches like the string of a bow. When the toes bend upwards at the end of a step, the fascia winds tight around the ball of the foot, raising the arch and turning the foot into a rigid lever, a trick called the windlass mechanism and described by the anatomist J. H. Hicks in 1954. When the foot lands, the arch flattens slightly and soaks up the shock.

Walking is a cycle repeated with every step. One leg's cycle begins at heel strike, rolls through mid-stance as the body vaults over the planted foot, and ends with toe-off as the calf muscles push from the ball of the foot and the big toe. The foot then swings forward through the air. The stance phase takes about 60 per cent of the cycle and the swing phase about 40, so for a moment in every stride both feet are on the ground. Biomechanists describe walking as an inverted pendulum: the body rises and falls over each leg, trading speed for height and back again, which saves much of the energy.

The forces are considerable. Each footfall presses on the ground with a little more than body weight when walking, and with two to three times body weight when running. Swinging the arms in opposition to the legs counters the twisting of the trunk, which is why walking with the arm and leg of the same side moving together feels so odd. The oldest direct evidence of upright walking comes from footprints at Laetoli in Tanzania, left in volcanic ash about 3.6 million years ago and uncovered by Mary Leakey's team in 1978. They show a heel strike and a big toe in line, much as ours do.

Did you know? About a quarter of all the bones in your body are in your feet: 52 of the 206.

Feet complain when the system is overloaded. Plantar fasciitis, irritation where the fascia attaches to the heel, causes sharp pain with the first steps of the morning. Flat feet, in which the inner arch is low or absent, are common and often cause no trouble at all, while bunions push the big toe sideways. Most of the time the foot's architecture goes unnoticed, carrying its owner thousands of steps a day on a platform the size of a paperback.

How Muscles Contract

The body has more than 600 skeletal muscles, making up around 40 per cent of body weight in a typical man and somewhat less in a typical woman. Each muscle is a bundle of bundles. Inside its sheath lie fascicles, and inside each fascicle hundreds of muscle fibres, long cells with many nuclei that can run for several centimetres. Each fibre is packed with myofibrils, and each myofibril is a chain of tiny repeating units called sarcomeres, about 2.5 thousandths of a millimetre long. The sarcomere is where movement actually happens.

Under a microscope, skeletal muscle looks striped. The stripes are overlapping arrays of two proteins: thin filaments of actin, anchored to the ends of each sarcomere at the Z-discs, and thick filaments of myosin in the middle, bristling with tiny heads. When a muscle contracts, neither filament gets shorter. Instead the myosin heads haul the actin filaments inwards, so the two slide past each other and the Z-discs are drawn together. This sliding filament theory was published in 1954 by two pairs working independently: Andrew Huxley and Rolf Niedergerke, and Hugh Huxley and Jean Hanson.

The sequence begins with a nerve. A motor neuron releases the chemical messenger acetylcholine where it meets the fibre, triggering an electrical wave that races along the membrane and down into the cell. That signal releases calcium from an internal store, the sarcoplasmic reticulum. Calcium shifts two blocking proteins, troponin and tropomyosin, off the binding sites on actin. Myosin heads latch on, swivel and pull the actin about 5 to 10 nanometres, or millionths of a millimetre: the power stroke. A molecule of ATP, the cell's energy currency, then detaches each head and re-cocks it for the next pull. Repeated many times a second across billions of heads, these tiny tugs add up to a lift or a leap. When the nerve falls silent, calcium is pumped back into store and the muscle relaxes.

The link between electricity and muscle was first shown in the 1780s by Luigi Galvani in Bologna, whose dissected frogs' legs twitched when touched with metal. Muscles can only pull, never push, so they work in opposing pairs: the biceps bends the elbow and the triceps straightens it. The stiffness of rigor mortis after death is the same machinery stalled: with no ATP left, the myosin heads stay locked onto actin until the proteins begin to break down.

Did you know? The body's longest muscle is the sartorius, a strap running from the hip across to the inside of the knee; its name comes from the Latin for tailor, after the cross-legged way tailors once sat.

Things go wrong when any link in the chain fails. In the muscular dystrophies, faulty genes leave fibres fragile so that they gradually break down; in myasthenia gravis the immune system blocks the acetylcholine signal, causing weakness that worsens with use. In everyday life the limit is usually fuel: when ATP cannot be replenished fast enough, force falls away. Every movement you make, from a blink to a sprint, is billions of molecular rowers pulling in time.

Tendons and Ligaments

Muscles and bones need connectors. Tendons join muscle to bone and transmit the pull of contraction; ligaments join bone to bone, holding joints together and stopping them moving too far. Both are dense, silvery-white cords made mostly of collagen, the body's most abundant protein, arranged in parallel bundles like the strands of a rope. Under a microscope the fibres have a wavy crimp, which straightens when the tissue is first stretched and gives a little before it goes taut.

For its size, tendon is formidably strong, able to withstand roughly a quarter of the tensile stress that breaks mild steel. The Achilles tendon, joining the calf muscles to the heel bone, is the thickest and strongest in the body, and during running it carries several times body weight with each stride. It is named after the Greek hero whose mother held him by the heel when she dipped him in the River Styx, leaving his one vulnerable spot. The name was coined by the Flemish anatomist Philip Verheyen in 1693.

Tendons are not only cables but springs. Stretched as the foot lands, the Achilles stores elastic energy and returns much of it as the foot pushes off, a principle explored by the British zoologist R. McNeill Alexander, who showed how kangaroos and running humans bounce on their tendons. Ligaments, by contrast, are built to restrain. The knee shows them at work. Two cruciate ligaments cross inside the joint, the anterior one stopping the shin from sliding forwards and the posterior one stopping it sliding back, while two collateral ligaments brace the inner and outer sides. Between the bones, two crescent-shaped pads of cartilage, the menisci, spread the load.

Both tissues have a poor blood supply, which gives them their pale colour and makes them slow to heal; a serious injury can take many months to mend. A sprain is a stretched or torn ligament, most often on the outside of the ankle when the foot rolls inwards. The anterior cruciate ligament commonly tears in sports that involve sudden pivots and landings, and female athletes are several times more likely to tear it than male athletes in the same sports. Repeated overload can also inflame or wear down a tendon, as in tennis elbow, which affects the tendon on the outside of the elbow and is far more common in people who never play tennis.

Did you know? Nobody is truly double-jointed. People who can bend their thumbs back to the wrist have ordinary joints with unusually stretchy ligaments, a trait called hypermobility.

Tendons and ligaments rarely get credit when things go right. Yet every jump, every jog down the stairs and every step of a long walk relies on them to transmit force, store energy and keep joints from coming apart. They are the body's rigging, and like a ship's rigging they are noticed mainly when one snaps.

Strength, Speed and Stamina

Muscles are not all alike, because each contains a mix of fibre types. Type I, or slow-twitch, fibres contract relatively slowly but tirelessly. They are packed with mitochondria, the cell's power stations, and with myoglobin, a red oxygen-storing protein, which is why they look dark. Type II, or fast-twitch, fibres contract several times faster and more forcefully but tire quickly; one subtype, IIa, keeps some endurance, while IIx is built for pure power. A roast chicken shows the difference: dark meat comes from legs used all day, white meat from breast muscles used in short bursts.

Most people's thigh muscles are roughly half slow and half fast fibres, but the mix varies. Biopsies of elite marathon runners have found calf muscles with around 80 per cent slow fibres, while top sprinters lean the other way. The proportions are largely inherited, although training can shift fibres between the fast subtypes and make all of them more capable.

Every contraction runs on ATP, but a muscle holds only enough for a couple of seconds of hard work, so it must be remade continuously. Three systems do this, overlapping at different speeds. For the first few seconds a reserve of phosphocreatine recharges ATP almost instantly; it powers a 100-metre sprint and is largely spent within about ten seconds. Next, anaerobic glycolysis breaks down glucose without oxygen, fast but limited, producing lactate; it dominates efforts of up to a couple of minutes, such as a 400-metre race. Beyond that, aerobic metabolism in the mitochondria burns sugars and fats with oxygen, slowly but almost without limit, powering a marathon. Over a day the body recycles roughly its own weight in ATP.

Much of this was first worked out by the British physiologist A. V. Hill, who shared a Nobel Prize in 1922 for measuring the heat muscles produce and describing the oxygen debt that runners build up. One popular idea has not survived: lactic acid does not cause the stiffness felt a day or two after hard exercise. That delayed soreness comes from microscopic damage in the fibres and the repair that follows, while lactate is cleared within an hour or so and is even used as fuel.

Did you know? A muscle's strength depends mainly on its cross-sectional area rather than its length, which is why trained muscles grow thicker, not longer.

Training reshapes muscle to the job. In the first weeks of strength training most gains are neural, as the nervous system learns to recruit more fibres at once; later the fibres themselves thicken. Endurance training multiplies mitochondria and capillaries instead. The extremes are impressive: Usain Bolt reached about 44 kilometres per hour during his 9.58-second 100 metres in 2009, and Kelvin Kiptum ran a marathon in 2 hours 0 minutes 35 seconds in 2023. From middle age muscle slowly declines, a loss called sarcopenia, but it responds to training at any age. Strength, speed and stamina are not three gifts but one tissue tuned three ways.

The Heart

Press two fingers just left of your breastbone and you can feel it: the heart, a hollow muscle about the size of a clenched fist, weighing roughly 250 to 350 grams in an adult. It sits in the middle of the chest between the lungs, wrapped in a tough double-layered bag, the pericardium, with its pointed lower tip, the apex, angled down and to the left. Its walls are made of cardiac muscle, a tissue found nowhere else, whose cells are branched, joined end to end and never tire in the way a sprinter's leg muscles do.

Inside, a wall called the septum divides the heart into two pumps sharing one body. Each side has a thin-walled receiving chamber on top, an atrium, and a thick-walled pumping chamber below, a ventricle. The right side takes in used blood from the body through the two venae cavae and sends it a short distance to the lungs. The left side receives fresh blood from the lungs and drives it out through the aorta to everything else. Because that second journey is far longer, the wall of the left ventricle is about a centimetre thick, roughly three times that of the right.

Four valves keep the traffic one way. The tricuspid and mitral valves guard the gateways from atria to ventricles, tethered by fine cords like the rigging of a parachute; the pulmonary and aortic valves sit at the exits. The familiar "lub-dub" is not the muscle at all but the sound of these valves snapping shut, first the inlet pair, then the outlet pair. At rest the heart moves around five litres of blood a minute, roughly 7,000 litres a day, and it beats about 100,000 times between one breakfast and the next.

Did you know? Heart muscle cells are renewed only very slowly: carbon-dating studies suggest about 1 per cent are replaced each year in young adults, and fewer in old age.

For centuries the heart was thought to warm the blood rather than pump it. The Arab physician Ibn al-Nafis described blood passing through the lungs in the 13th century, and in 1628 the English doctor William Harvey published De motu cordis, showing by careful arithmetic that the heart pumps far more blood in an hour than the body could possibly make, so the same blood must go round and round.

The heart feeds itself first, through the coronary arteries that crown its surface. When one of them is blocked, the muscle beyond it is starved of oxygen; that is a heart attack. Faulty valves can leak or stiffen and make an extra whooshing sound, a murmur, that a doctor can hear through a stethoscope. Over a long life the heart will beat around three billion times without a single day off.

The Heartbeat

Every heartbeat begins with a spark the size of a grain of rice. In the wall of the right atrium sits the sinoatrial node, a small cluster of specialised muscle cells that fire on their own, with no instruction from the brain. Their membranes slowly leak positive ions until they reach a threshold and discharge, then reset and start again. At rest this natural pacemaker fires around 60 to 100 times a minute in most adults, and each discharge becomes one beat.

The electrical wave sweeps across both atria in about a tenth of a second, squeezing them so that they top up the ventricles below. Then it meets an insulating ring of tissue between upper and lower chambers. The only way through is the atrioventricular node, which holds the signal back for around a tenth of a second, just long enough for the ventricles to fill. From there the impulse races down the bundle of His in the septum, splits into left and right branches and spreads through the Purkinje fibres in the ventricle walls. The ventricles contract from the apex upwards, wringing blood towards the exits like toothpaste squeezed from the bottom of the tube.

The heart sets its own rhythm, but the nervous system can turn the dial. Signals along the vagus nerve slow the pacemaker, while adrenaline and sympathetic nerves speed it up, which is why your pulse climbs when you run for a bus and falls as you settle into a chair. A fit endurance athlete may rest at 40 beats a minute, because each powerful beat moves more blood.

Did you know? A transplanted heart arrives with its nerves cut, so it beats faster than normal at rest and speeds up during exercise only as adrenaline reaches it through the blood.

The tiny currents of each beat reach the skin, and in 1903 the Dutch physiologist Willem Einthoven recorded them reliably with a sensitive string galvanometer, work that earned him the Nobel Prize in 1924. His letters are still used on every electrocardiogram, or ECG: the small P wave as the atria fire, the tall QRS spike as the ventricles fire, and the gentle T wave as they recover.

When the wiring misfires, the rhythm falters. In atrial fibrillation the atria quiver chaotically and the pulse becomes irregular; in ventricular fibrillation the main chambers merely tremble and pump nothing, which is a cardiac arrest. A defibrillator delivers a shock that silences the chaos so the sinoatrial node can take charge again, and since 1958, when the first fully implanted pacemaker was fitted in Sweden, small devices have stood in for failing nodes. The occasional "skipped" beat most people notice is usually a harmless early beat. Your rhythm section has been keeping time since about six weeks after conception.

Arteries, Veins and Capillaries

Lay all the blood vessels of an adult end to end and the line is often said to stretch around 100,000 kilometres, more than twice round the Earth. The figure is a rough estimate, but the point is sound: almost no cell in the body is more than a hair's breadth from a supply line. The network has three kinds of vessel, each built for its job.

Arteries carry blood away from the heart under high pressure. Their walls have three layers: a smooth inner lining of flat cells, the endothelium; a thick middle coat of smooth muscle and elastic fibres; and a tough outer sheath. The aorta, the largest, is about 2.5 centimetres across. Its elastic wall stretches with each beat and recoils between beats, smoothing the surge into a steady flow, and that ripple is the pulse you feel at your wrist. Arteries branch into ever narrower arterioles, whose muscular walls tighten or relax to steer blood where it is needed, flushing the skin of a blusher or the gut after lunch.

The arterioles feed the capillaries, the real point of the whole system. Each is only 5 to 10 micrometres wide, so narrow that red blood cells pass in single file and must bend to squeeze through, and its wall is a single cell thick. Oxygen, glucose and other nutrients seep out through it into the tissues, while carbon dioxide and wastes seep in. Blood slows almost to a crawl here, giving the exchange time to happen.

Capillaries merge into venules and then veins, which carry blood back to the heart at low pressure. Their walls are thinner and floppier, and at any moment they hold roughly two-thirds of all your blood. In the limbs, cup-shaped valves stop it sliding backwards, and the squeeze of surrounding muscles pushes it upwards each time you move. William Harvey demonstrated these valves in 1628 by pressing on the veins of a bandaged arm, and in 1661 Marcello Malpighi, peering through a microscope at a frog's lung, saw the capillaries that completed Harvey's circle.

Did you know? Veins are not full of blue blood. Blood is always red, darker when it is low in oxygen; veins look blue because skin scatters and absorbs red light more than blue.

When vessels fail, the effects are familiar. Fatty plaques can narrow arteries, a process called atherosclerosis. Worn-out valves let blood pool, stretching leg veins into knotted varicose veins, and a clot in a deep leg vein can form when the muscle pump stops on a long flight. It is also why soldiers standing still on parade sometimes faint: without the muscle pump, blood collects in the legs. Keep moving, and your veins keep up.

Blood

An adult carries roughly five litres of blood, about 7 to 8 per cent of body weight, and it makes the full round trip from the heart to the toes and back in about a minute. It looks like a simple red liquid, but leave a tube of it spinning in a centrifuge and it separates into layers like a cocktail. At the top, about 55 per cent of the volume, is a pale straw-coloured fluid, plasma. At the bottom, about 45 per cent, are packed red blood cells. In between lies a thin whitish film, the buffy coat, which holds the white blood cells and platelets.

Plasma is more than 90 per cent water, and it is the body's delivery van. It carries dissolved glucose, salts, fats and amino acids from the gut, hormones from the glands, and wastes such as urea to the kidneys. It also holds proteins: albumin, which keeps water from leaking out of the vessels, antibodies for defence, and fibrinogen, the raw material of a clot. The cells have their own jobs. Red cells, by far the most numerous, ferry oxygen. White cells, fewer than one cell in a thousand, patrol for invaders. Platelets, tiny cell fragments, stand by to seal leaks.

All of these cells are made in the red bone marrow, in the flat bones of the hips, breastbone, ribs and skull, and the ends of long bones, which turns out around two million red cells every second. A microlitre of blood, a drop smaller than a pinhead, contains roughly five million red cells, a few thousand white cells and around 150,000 to 400,000 platelets.

Did you know? Blood is thicker than water in a literal sense: it is around three to five times more viscous, mostly because of the crowd of red cells it carries.

Blood also does quieter work. It spreads heat from busy muscles and the liver to the skin, and it is held at a slightly alkaline pH of 7.35 to 7.45; even a small drift either way disturbs the body's chemistry. The Dutch draper Antonie van Leeuwenhoek described red "globules" through his home-made microscopes in the 1670s, after Jan Swammerdam had seen them in frog blood.

When blood goes wrong, the trouble spreads everywhere it goes. Too few red cells or too little haemoglobin is anaemia, which brings tiredness and breathlessness. Cancer of the blood-forming cells is leukaemia. A blood donation in the UK takes about 470 millilitres, and the body replaces the lost plasma within a day or two and the red cells within a few weeks. That is the remarkable thing about this river: it is being rebuilt all the time, while it flows.

Red Blood Cells

Red blood cells are the most numerous cells in the body. An adult has around 25 trillion of them, roughly four in every five human cells, and each is a tiny doughnut without a hole: a biconcave disc about 7.5 micrometres across and 2 micrometres thick, dimpled on both faces. That shape gives a large surface for gases to cross and lets the cell fold almost in half to slip through capillaries narrower than itself. To make room for its cargo, a mammalian red cell gives up its nucleus and its mitochondria as it matures. It cannot divide or repair itself; it is a bag built for one task.

The cargo is haemoglobin, an iron-containing protein packed about 270 million molecules to a cell. Each molecule has four chains, and each chain cradles a haem group with an iron atom at its centre that can hold one molecule of oxygen, so a single haemoglobin carries four. Bound to oxygen in the lungs, haemoglobin turns bright scarlet; having released it in the tissues, it turns a darker maroon. In 1959 the Austrian-born chemist Max Perutz, working in Cambridge, worked out its three-dimensional structure by X-ray crystallography after more than twenty years of effort, sharing a Nobel Prize in 1962.

A red cell's life lasts about 120 days. It is born in the red bone marrow, where a hormone from the kidneys, erythropoietin, raises production whenever oxygen runs low, as it does at high altitude. During its life it makes something like 170,000 circuits of the body. As it ages, its membrane stiffens, and the spleen and liver act as quality control: large white cells called macrophages swallow the worn-out cells. The iron is saved and returned to the marrow, while the haem is broken down into yellow bilirubin, which the liver sends out in bile.

Did you know? The changing colours of a bruise are haemoglobin being dismantled on the spot: purple-blue, then green from biliverdin, then yellow from bilirubin.

Faults in red cells are among the best understood diseases. In 1949 Linus Pauling and colleagues showed that sickle cell disease is caused by an abnormal haemoglobin, the first illness traced to a single altered molecule; one changed amino acid makes the protein clump when oxygen is low, bending cells into rigid crescents that block small vessels. Carrying one copy of the gene gives some protection against malaria, which is why it is common where malaria is. Lack of iron, the commonest cause of anaemia worldwide, leaves cells small and pale. Every second you replace about two million red cells, and every second about two million are retired: a quiet production line of extraordinary reliability.

Blood Groups

For centuries blood transfusion was a gamble that usually went wrong. Some early experiments in the 1660s even used lamb's blood. The reason became clear only in 1901, when the Austrian doctor Karl Landsteiner, working in Vienna, mixed the red cells and serum of his colleagues and saw that some combinations clumped while others did not. He sorted people into three groups, now called A, B and O; a fourth, AB, was found a year later. The discovery earned Landsteiner a Nobel Prize in 1930 and made safe transfusion possible.

The groups depend on antigens, molecular flags on the surface of every red cell. In the ABO system they are short chains of sugars. Group A cells carry the A flag, group B cells the B flag, group AB cells carry both, and group O cells carry neither. The twist is in the plasma. From early infancy, each person makes antibodies against the flags they lack: someone with group A has anti-B in their plasma, group B has anti-A, group O has both, and group AB has neither. Give the wrong cells and the antibodies latch on, the cells clump and burst, and the result can be a dangerous transfusion reaction.

The second key system is Rhesus, named after the rhesus monkeys used in experiments by Landsteiner and Alexander Wiener around 1940. People whose cells carry the RhD antigen are "positive"; those without it are "negative", about 15 per cent of people of European ancestry. Unlike anti-A and anti-B, anti-D antibodies appear only after exposure, for instance when a Rhesus-negative mother carries a Rhesus-positive baby. In a later pregnancy her antibodies can cross the placenta and attack the baby's red cells, a condition now largely prevented by giving the mother anti-D injections.

Did you know? In 1952 doctors in Mumbai found people with the rare Bombay blood group, who lack even the basic H antigen and can safely receive only Bombay blood.

These rules explain the famous labels. Group O negative red cells carry no A, B or D flags, so in an emergency they can be given to almost anyone; group AB positive patients can receive red cells of any ABO and Rhesus group. For plasma the logic flips, and AB plasma is the universal gift. In the UK nearly half of people are group O and AB is the rarest, at about 3 per cent, though proportions vary around the world.

Today more than 40 blood group systems are recognised, and hospital laboratories cross-match donor and patient blood before a planned transfusion. One popular belief does not survive scrutiny: the idea, fashionable in Japan, that blood type shapes your personality has no scientific support. Your blood group tells a stranger whether your blood is safe to share, and nothing about whether you will be good company.

Clotting

Nick a finger with a kitchen knife and the bleeding usually stops within a few minutes, without a thought from you. That ordinary miracle is haemostasis, the stopping of blood, and it has to be finely judged: too little and a small wound becomes dangerous, too much and blood sets solid inside a healthy vessel. The body solves the problem with a fast response that switches on only where the damage is, in a sequence of overlapping stages.

First, the injured vessel clamps down. Its smooth muscle contracts in a vascular spasm that narrows the opening and slows the flow within seconds. Second, platelets arrive. These are fragments, only 2 to 3 micrometres across, broken off giant cells in the bone marrow, and they live for about 7 to 10 days. Normally they slide past the smooth lining of the vessel, but a cut exposes the collagen beneath. Platelets stick to it, change from smooth discs into spiky shapes and release chemicals that call in more platelets, which pile on to form a soft platelet plug.

Third comes the coagulation cascade, a chain of a dozen or so clotting factors, mostly proteins made by the liver and numbered with Roman numerals. Each activated factor switches on many molecules of the next, so a small trigger is amplified into a flood. At the end of the chain an enzyme called thrombin cuts the soluble plasma protein fibrinogen into sticky threads of fibrin. The threads knit into a mesh over the plug and trap red cells, turning the liquid at the wound into a firm red gel. Several of the factors need vitamin K to be made. Finally the clot shrinks, pulling the edges of the wound together, and once the vessel has healed an enzyme called plasmin dissolves it.

Did you know? DNA from the remains of Russia's last royal family showed in 2009 that the young heir Alexei had haemophilia B, inherited through his mother from Queen Victoria.

The cascade was pieced together over decades: Paul Morawitz proposed a classic four-factor scheme in 1905, and in 1964 two groups, Robert Macfarlane in Oxford and Earl Davie with Oscar Ratnoff in the United States, described the step-by-step amplifying cascade. People with haemophilia lack one factor, usually factor VIII or IX, and can bleed for long periods after small injuries; because the genes lie on the X chromosome, it mostly affects boys. The opposite problem, thrombosis, is a clot where none is wanted, in a leg vein, a coronary artery or the brain.

On the skin, the outer layer of a clot dries into a scab, a temporary roof while new tissue grows underneath. Pick it off and you simply restart the cascade. The healing beneath it belongs to another chapter; the clot's job is done the moment the leak is sealed.

Blood Pressure

In 1733 the English clergyman and scientist Stephen Hales tied a mare on her back, opened an artery in her neck and connected it to a glass tube about three metres long. The blood rose roughly two and a half metres up the tube and bobbed with each heartbeat. It was the first measurement of blood pressure, the force that blood exerts on the walls of its vessels, and it showed that the arteries are never at rest.

Pressure in the arteries rises and falls with every beat. The peak, as the left ventricle contracts and pushes blood into the aorta, is the systolic pressure; the trough, while the heart refills, is the diastolic pressure. Both are given in millimetres of mercury, after the old mercury columns, so a typical healthy young adult reading of "120 over 80" means the pressure could push a column of mercury 120 millimetres high at the peak and 80 between beats. The modern cuff method dates from 1896, when Scipione Riva-Rocci used an inflatable band round the arm, and from 1905, when the Russian surgeon Nikolai Korotkov described the tapping sounds heard through a stethoscope as the cuff deflates.

Pressure is not the same everywhere. It is highest in the aorta and falls along the way, most steeply in the muscular arterioles, which act like taps controlling resistance. By the time blood reaches the capillaries the pressure is around 35 at the arterial end and 15 at the venous end, and in the great veins near the heart it is only a few millimetres. At any moment the pressure depends on how much the heart pumps and how tightly the arterioles are squeezed.

Did you know? A giraffe needs a blood pressure roughly twice ours to lift blood two metres up its neck to its brain.

The body keeps the pressure within limits second by second. Stretch sensors called baroreceptors, in the wall of the aorta and the carotid arteries of the neck, report to the brainstem, which adjusts heart rate and vessel width. Stand up quickly and blood briefly pools in the legs; the reflex usually catches it within a heartbeat or two, but if it lags you feel light-headed. Over hours and days the kidneys take over, by adjusting how much salt and water the body keeps.

Persistently high pressure, hypertension, usually causes no symptoms, which is why it is often called a silent condition. In the UK a clinic reading of 140 over 90 or above is generally regarded as high. Over years it strains the heart and damages arteries, raising the risk of stroke, heart attack and kidney disease. Readings also vary naturally across the day and often climb in a doctor's surgery, the so-called white-coat effect. A single number never tells the whole story; the trend over time does.

The Lymphatic System

Blood vessels leak, and they are meant to. As blood passes through the capillaries, pressure pushes fluid out between the cells, bathing the tissues in nutrients. Most of it seeps back in at the far end of the capillary, but not all. Every day roughly three litres are left behind, along with stray proteins and cells. Without a way to collect it, the tissues would swell like sponges. The job of mopping up falls to the lymphatic system, a second network of vessels that runs alongside the blood vessels almost everywhere.

It begins with blind-ended lymphatic capillaries, slightly larger than blood capillaries, whose overlapping wall cells act like one-way flaps that let fluid in but not out. Once inside, the fluid is called lymph, clear and pale. The capillaries join into larger vessels, which have valves like veins. There is no pump: lymph is pushed along by the squeeze of muscles, the pulse of nearby arteries and the pressure changes of breathing. In the lining of the small intestine, special lymphatics called lacteals absorb fats from digested food, turning the lymph there milky.

Along the way the lymph passes through lymph nodes, bean-shaped filters usually a few millimetres to about 2 centimetres long. An adult has several hundred of them, often quoted as around 600, clustered in the neck, armpits, groin, chest and abdomen. Inside, packed white blood cells inspect the passing fluid and trap bacteria, viruses and debris. Finally the vessels merge into two main channels. The thoracic duct, about 40 centimetres long, drains most of the body and empties into a large vein at the base of the neck on the left, while the small right lymphatic duct drains the right arm, chest and head.

The system has two more organs. The spleen, about the size of a fist, sits under the ribs on the upper left; it filters blood rather than lymph, retiring old red cells and storing white cells. The thymus, behind the breastbone, is where young T cells are trained; it is largest in childhood and gradually shrinks into fat. The Italian anatomist Gaspare Aselli first noticed the milky lacteals in 1622 in a dog that had just been fed, and in the 1650s Olof Rudbeck and Thomas Bartholin traced the wider network.

Did you know? Lymphatic vessels in the membranes around the brain were described only in 2015, overturning the textbook view that the brain had none.

When nodes are removed or damaged, for example after some cancer operations, lymph can build up and cause lasting swelling, called lymphoedema. The "swollen glands" in your neck during a sore throat are not glands at all but lymph nodes, swollen because they are busy. A quiet drainage system most of the time, it becomes a battlefield the moment a germ gets in.

The Kidneys

Tuck your hands on your waist with thumbs pointing back and they rest just below your kidneys, a pair of bean-shaped organs pressed against the back wall of the abdomen on either side of the spine. Each is about 11 to 12 centimetres long, the size of a computer mouse, and weighs around 150 grams; the right one sits a little lower, nudged down by the liver. Together they make up less than half a per cent of body weight, yet they receive about a fifth of all the blood the heart pumps.

Slice a kidney lengthways and you see an outer layer, the cortex, and an inner region, the medulla, arranged in cone-shaped pyramids that drain into a funnel, the renal pelvis, and on into the ureter. The working units are microscopic nephrons, typically about a million in each kidney, though the number varies widely between people. Each nephron starts with a glomerulus, a knot of capillaries cupped inside a double-walled pouch named after William Bowman, who described it in 1842. Blood pressure forces water and small molecules out of the glomerulus, leaving blood cells and large proteins behind.

The kidneys filter about 180 litres of fluid a day, but you pass only about one to two litres of urine. The rest is reclaimed as the filtrate runs along the nephron's tubule. The first, coiled stretch, the proximal tubule, takes back all the glucose and around two-thirds of the salt and water. The hairpin loop of Henle dips into the medulla and builds up a gradient of salt that lets water be drawn out later. The distal tubule fine-tunes salts and acidity, and in the collecting duct a hormone from the pituitary gland, antidiuretic hormone, decides how much water is kept: plenty when you are thirsty, little after a large drink. What is left, carrying urea and other wastes, becomes urine.

Did you know? At around 180 litres a day, the kidneys filter the whole volume of your blood plasma about 60 times every day.

The kidneys do more than clean. They balance salt and water, which helps set blood pressure, and they release erythropoietin, which tells the marrow to make red cells, and activate vitamin D. When they fail, wastes build up in the blood. In 1943 in the occupied Netherlands the Dutch doctor Willem Kolff built the first working artificial kidney, a dialysis machine improvised partly from sausage casing and a drum. In 1954, in Boston, Joseph Murray's team performed the first successful kidney transplant, between identical twins, Richard and Ronald Herrick.

Most people can live normally with one healthy kidney, which is why living donation is possible. The colour of your urine is a rough guide to the kidneys at work: pale after a long drink, darker after a hot, dry day. Two small beans, quietly deciding what in your blood stays and what goes.

The Airways

The airways are the tubes that carry air from the outside world to the lungs, and they do far more than simply let it through. The route starts at the nostrils and the nasal cavity, a tall, narrow chamber whose side walls carry three curled shelves of bone called turbinates (or conchae). Behind it lies the pharynx, the throat, shared by food and air; then the larynx, or voice box; then the trachea, the windpipe, a tube about 10 to 12 centimetres long and roughly 2 centimetres wide that runs down the front of the neck into the chest.

The turbinates make the incoming air swirl past a large area of warm, wet lining packed with blood vessels. By the time a breath reaches the lungs it has been heated to body temperature and is almost fully saturated with water vapour, whether you inhaled it on a ski slope or in a desert. Hairs at the nostrils catch coarse particles, and a sticky layer of mucus traps finer dust, pollen and microbes. At the top of the larynx, a leaf-shaped flap called the epiglottis tips down when you swallow, steering food behind the windpipe into the oesophagus.

The trachea is held open by 16 to 20 C-shaped rings of cartilage, with the open part of each C facing backwards against the oesophagus. You can feel the rings as ridges below your Adam's apple. At about the level of the fourth or fifth thoracic vertebra, the trachea forks at a ridge called the carina into the left and right main bronchi. The right bronchus is wider, shorter and steeper than the left, which is why an inhaled peanut usually ends up on the right. In 1897 the German surgeon Gustav Killian looked down a living windpipe with a tube and a light and pulled out a pork bone lodged in a farmer's bronchus, the first bronchoscopy.

All along the way, the lining is carpeted with cilia, microscopic hairs that beat 10 to 20 times a second in coordinated waves. They push the mucus layer steadily upwards, a "mucus escalator" that delivers trapped grime to the throat to be swallowed, unnoticed, many times a day. Tobacco smoke slows and eventually destroys the cilia, which is why smokers have to cough up what their escalator no longer carries. In asthma, the smooth muscle around the smaller airways tightens and the lining swells, narrowing the tubes so that breathing out becomes a wheezing effort.

Did you know? Most people breathe mainly through one nostril at a time; the other side swells slightly, and the two swap every few hours in a rhythm called the nasal cycle.

A runny nose on a cold day is the system working overtime: the lining pours out extra moisture to warm the freezing air, and some of it condenses before it can be reabsorbed. The airways are not plumbing but an air-conditioning plant that never switches off.

The Lungs

The lungs are a pair of soft, spongy, cone-shaped organs that fill most of the chest, from just above the collarbones down to the dome of the diaphragm. Together they weigh only about a kilogram, because most of their volume is air. They are not identical. The right lung has three lobes, upper, middle and lower, while the left has only two, and carries a scoop called the cardiac notch to make room for the heart, which leans to the left.

Inside, the lungs are built around the bronchial tree. The trachea divides into two main bronchi, these into lobar bronchi, then segmental bronchi, and so on, each tube splitting into two smaller ones about 23 times in all. The first fifteen or sixteen generations form the conducting zone: bronchi stiffened with cartilage, then narrower bronchioles wrapped in smooth muscle. They carry air but exchange no gas, and their volume, about 150 millilitres, is called the dead space. From around generation 17 the walls begin to bulge with air sacs, and by generation 23 the tree ends in millions of tiny alveolar sacs where oxygen finally enters the blood.

The lungs have no muscle of their own to move air. Each is wrapped in a thin membrane, the pleura, and the inside of the chest wall is lined by another. Between them lies a film of fluid only a hundredth or two of a millimetre thick, which lets the surfaces slide but makes them cling together, as two wet panes of glass do. When the chest expands, the lungs are pulled open with it. At rest an adult moves about half a litre of air per breath, 12 to 20 times a minute, which adds up to well over 15,000 breaths a day. A full breath can bring the total lung volume to around six litres in a large adult man, and even after the hardest exhalation more than a litre stays behind, so the lungs never empty.

Their importance was demonstrated dramatically in 1667, when Robert Hooke kept an anaesthetised dog alive by blowing air through its opened lungs with bellows. It was the fresh air, he showed, not the motion of the lungs, that kept the animal living. The lungs face the outside world with every breath, so they are exposed to infection: in pneumonia the air spaces fill with fluid and cells. If air leaks between the two pleural layers, in a pneumothorax, the seal breaks and the lung collapses like a released balloon.

Did you know? A piece of healthy lung floats in water. For centuries coroners used this "float test" to judge whether a newborn had ever breathed, a method now known to be unreliable.

You feel all this whenever you take a deep breath in a swimming pool and bob higher in the water. Your lungs are a buoyancy aid, a branching tree and a bellows, all at once.

Alveoli: Where Air Meets Blood

At the very ends of the bronchial tree lie the alveoli, tiny air sacs clustered like bunches of grapes around the final airways. Each is about a fifth of a millimetre across, and a careful count of adult lungs found around 480 million of them, though the number varies from person to person. Spread out flat, their inner surface would cover around 70 square metres, close to the floor of a badminton court, all folded into a space the size of a pair of footballs.

Each alveolus is wrapped in a mesh of capillaries so dense that blood flows over it almost as a continuous sheet. Between the air and the blood lies the blood–air barrier, which is only about half a micrometre thick, more than a hundred times thinner than a human hair. It has three layers: a flat type I cell lining the air sac, a shared basement membrane, and the thin cell of the capillary wall. Oxygen simply diffuses across, from high concentration in the air to low concentration in the blood, while carbon dioxide diffuses the other way. At rest a red blood cell spends about three quarters of a second in an alveolar capillary, yet it is usually fully loaded within the first third of that time, leaving a safety margin for exercise.

Wet surfaces like these have a problem: surface tension, the force that makes water form drops, pulls small bubbles closed. Rounder, plumper type II cells solve it by secreting surfactant, a detergent-like film of fats and proteins that lowers surface tension and keeps the alveoli from collapsing each time you breathe out. Patrolling the surface are alveolar macrophages, nicknamed dust cells, which swallow inhaled particles and bacteria.

Marcello Malpighi first saw alveoli and the capillaries around them in 1661, looking at frog lungs under an early microscope, and in doing so found the missing link between arteries and veins. Nearly three centuries later, in 1959, Mary Ellen Avery and Jere Mead showed that premature babies who struggled to breathe lacked surfactant, an insight that led to treatments now saving many newborn lives. In adults, emphysema, usually caused by smoking, breaks down the walls between alveoli, merging them into larger, floppier spaces with far less surface for gas exchange. In pulmonary fibrosis the barrier thickens and stiffens instead.

Did you know? At any moment the capillaries of your lungs hold only about 75 millilitres of blood, roughly five tablespoons, spread so thin that it coats the entire alveolar surface.

Blowing a soap bubble shows the physics at work: the smaller the bubble, the harder it is to inflate. A newborn's first breath, opening millions of fluid-filled alveoli at once, is one of the hardest breaths of a lifetime. After that, surfactant makes every breath feel effortless.

The Diaphragm and Breathing

The diaphragm is a dome-shaped sheet of skeletal muscle that separates the chest from the abdomen. Its muscle fibres run from the lower ribs, the breastbone and the spine up to a flat central tendon at the top of the dome, on which the heart sits. It is pierced by three large openings, for the oesophagus, the aorta and the main vein returning blood from the lower body. Its nerve, the phrenic nerve, starts high in the neck from the third, fourth and fifth cervical spinal nerves, a fact medical students remember with the rhyme "C3, 4 and 5 keep the diaphragm alive".

Breathing in is active work. When the diaphragm contracts, its dome flattens and moves down, by about one or two centimetres in quiet breathing and up to ten centimetres in a deep breath. At the same time the external intercostal muscles between the ribs lift the rib cage up and out, like the handle of a bucket swinging upwards. The chest grows larger, and because the lungs cling to its walls, they expand too. By Boyle's law, gas in a larger space is at lower pressure: the air in the lungs drops just a little, about one millimetre of mercury, below the air outside. That small difference is enough, and air flows in.

Breathing out, at rest, needs no effort at all. The diaphragm relaxes, the stretched lungs and chest wall spring back by elastic recoil, and air is pushed out. Only when you blow out candles, shout or run do the internal intercostals and the abdominal muscles join in to squeeze air out faster. In quiet breathing the diaphragm does about three quarters of the work. The rhythm itself comes from a cluster of neurons in the brainstem that fires automatically, day and night, though you can override it at will to speak, sing or sigh.

The mechanics were argued out in the seventeenth century. In the 1670s the English physician John Mayow described the chest as a bellows: it does not suck air in, he reasoned, but enlarges, and the outside air presses in to fill the space. When the phrenic nerves are damaged, or the spinal cord is injured high in the neck, the diaphragm can be paralysed and a machine may have to do its work.

Did you know? Babies hiccup in the womb. Unborn babies' hiccups are common in the last months of pregnancy, and many mothers can feel them as small rhythmic jolts.

Hiccups themselves are the diaphragm misfiring: a sudden involuntary contraction pulls air in, and a fraction of a second later the vocal folds snap shut, making the "hic". Most bouts stop on their own within minutes. Every other breath you take is quieter, a muscle pulling down and then simply letting go.

Oxygen and Carbon Dioxide

Every cell in the body burns fuel with oxygen and releases carbon dioxide as waste, and breathing exists to keep both gases moving. At rest an adult takes up about 250 millilitres of oxygen a minute and gives off about 200 millilitres of carbon dioxide. The engine that pulls them along is not a pump but a slope of partial pressure, the share of the total air pressure due to one gas. A gas always diffuses from where its partial pressure is higher to where it is lower.

Air is about 21 percent oxygen, so at sea level its oxygen pressure is about 160 millimetres of mercury. By the time air reaches the alveoli it has been diluted with water vapour and with carbon dioxide leaving the blood, and the oxygen pressure has fallen to about 100. Blood leaving the lungs carries an oxygen pressure of about 95, but most of its oxygen is not dissolved at all. About 98 percent rides on haemoglobin, the protein that fills red blood cells; each molecule can carry four oxygen molecules, and arterial blood is about 98 percent saturated. In the tissues, where oxygen pressure is around 40 and inside the mitochondria just a few, haemoglobin lets go. Even so, blood returning to the heart at rest is still about three quarters saturated, a large reserve for exercise.

Carbon dioxide makes the return journey by three routes. About 70 percent is turned into bicarbonate inside red blood cells, a reaction sped up enormously by the enzyme carbonic anhydrase; around 20 percent hitches a ride on haemoglobin; and the rest travels dissolved in plasma. In busy tissues, rising carbon dioxide and acid make haemoglobin release its oxygen more readily, the Bohr effect, so the hardest-working muscles automatically get the most.

The story of how we found out runs through the 1770s. Carl Wilhelm Scheele in Sweden and Joseph Priestley in England each isolated oxygen, and Antoine Lavoisier in Paris named it and showed that breathing is a slow combustion, like a candle burning inside us. Joseph Black had already found "fixed air", carbon dioxide, in exhaled breath. The chemistry can be hijacked: carbon monoxide binds haemoglobin roughly 200 times more tightly than oxygen, quietly blocking delivery. And a popular myth deserves correcting: blood in veins is never blue; it is dark red, and only looks bluish through the skin.

Did you know? When you lose fat, most of its mass leaves your body as carbon dioxide, breathed out through your lungs; only a smaller share leaves as water.

Exhaled air still contains about 16 percent oxygen, which is why rescue breaths can keep another person alive. With every breath out you are returning to the air most of what you borrowed, and a little of what you ate.

The Voice

The voice begins in the larynx, the voice box, a hollow framework of cartilage at the top of the windpipe. Its largest piece, the thyroid cartilage, juts forward to form the Adam's apple. Stretched across the inside, from front to back, are the two vocal folds, often called vocal cords, although they are not cords but rounded shelves of muscle and ligament covered in soft lining. In adult men they are roughly 17 to 25 millimetres long, in women about 12 to 17. Small pyramid-shaped arytenoid cartilages at the back swing the folds apart for breathing, opening a V-shaped gap called the glottis, and draw them together for speech.

Sound is made step by step. The folds close; air pressure from the lungs builds below them until it pushes them apart, opening from the bottom edge first; a puff of air escapes; then the elastic folds and the sudden drop in pressure in the fast-moving stream pull them shut again. The cycle repeats a hundred or more times every second, chopping the steady breath into a buzz. Tighten and stretch the folds, mainly with the cricothyroid muscle, and they vibrate faster, raising the pitch. A typical adult man speaks at around 120 vibrations a second, a woman at around 210, and young children higher still.

That raw buzz would sound like a duck call. The vocal tract above it, the throat, mouth and nasal cavity, works as a resonating chamber whose shape picks out certain frequencies; moving the tongue and jaw changes those resonances and turns the buzz into different vowels. The tongue, teeth, lips and soft palate then interrupt and shape the flow into consonants.

The first person to watch his own vocal folds at work was a singing teacher, Manuel García. In 1854, in London, he used a dentist's mirror on a long handle, a hand mirror and sunlight to see his larynx, the birth of laryngoscopy. Problems follow overuse and infection: in laryngitis the folds swell and the voice turns hoarse or vanishes, and singers and teachers who strain their voices can develop small calluses called vocal nodules. At puberty, the male larynx grows quickly, the folds lengthen and thicken, and the voice drops by about an octave, sometimes cracking on the way.

Did you know? When a soprano sings a top C, her vocal folds open and close more than a thousand times every second.

If your voice sounds strange on a recording, that is not the microphone's fault. You normally hear yourself partly through the bones of your skull, which favour the low tones; the recording is the voice everyone else hears. It is your breath, shaped into sound.

Coughs, Sneezes and Yawns

Coughs, sneezes and yawns are reflexes: breathing manoeuvres run by circuits in the brainstem rather than by conscious choice. You can sometimes delay one, rarely stop it, and never quite make a convincing fake. All three follow a similar script, a deep breath in, a pause, and a sudden or prolonged release, but they serve different ends.

A cough guards the lower airways. It starts when irritant receptors in the larynx, trachea or bronchi detect dust, mucus, smoke or a crumb going the wrong way, and send signals up the vagus nerve. The brainstem responds with a deep breath in. Then the glottis, the gap between the vocal folds, slams shut, and the abdominal and chest muscles contract hard against it, driving pressure inside the chest far above normal. When the glottis suddenly opens, air bursts out at high speed, dragging mucus and debris with it. The squeeze also narrows the windpipe, which speeds the blast further.

A sneeze does the same job for the nose. Irritation of the nasal lining is relayed by the trigeminal nerve, the large nerve of facial sensation, to a sneeze centre in the brainstem. A deep breath follows, the chest squeezes, and the tongue and soft palate adjust so the blast is channelled through the nose as well as the mouth. The eyes close by reflex, but contrary to a popular myth, they would not pop out if they stayed open. The famous claim that a sneeze leaves at over 100 miles an hour is also an exaggeration; high-speed filming suggests a few metres a second, though the turbulent cloud can carry droplets several metres.

The yawn is the odd one out: a long, slow inhalation with the jaw stretched wide, a brief peak, and a shorter exhalation, about six seconds in all. Its purpose is still debated. The old idea that yawning tops up oxygen was tested in the 1980s by the psychologist Robert Provine, who found that breathing extra oxygen or carbon dioxide did not change how often people yawned. One current idea is that it helps cool the brain; another links it to shifts between sleep and alertness. Yawns are famously contagious between people, and unborn babies yawn in the womb.

Did you know? For somewhere between one in six and one in three people, stepping into bright sunlight triggers a sneeze, a harmless quirk called the photic sneeze reflex.

Problems arise when a reflex will not switch off: a chronic cough that lasts for weeks deserves investigation, because the trigger may be anything from asthma to acid reflux. Most of the time, these are small acts of housekeeping. Even reading about yawning may make you yawn, which is the brainstem's way of having the last word.

Breathing at Altitude

Climb a mountain and the air does not run short of oxygen as a share: it is still about 21 percent oxygen at the top of Everest. What falls is the air pressure, and with it the partial pressure of oxygen, the push that drives oxygen across the alveoli into the blood. Air pressure halves at around 5,500 metres. On the summit of Everest, at 8,849 metres, it is only about a third of its sea-level value, and the oxygen pressure of the air falls from about 159 to about 53 millimetres of mercury.

The body responds in stages. Within minutes, sensors called the carotid bodies, tiny clusters of cells in the neck where the carotid arteries fork, detect the fall in blood oxygen and drive faster, deeper breathing, while the heart speeds up. Breathing harder blows off carbon dioxide and makes the blood more alkaline, so over the next few days the kidneys excrete extra bicarbonate to rebalance it. Over weeks, the kidneys also release more of the hormone erythropoietin, which tells the bone marrow to make more red blood cells, raising the blood's carrying capacity. This acclimatisation is why climbers ascend slowly and why the rule "climb high, sleep low" exists.

Going up too fast has consequences. Above about 2,500 metres, many people develop acute mountain sickness: headache, nausea, poor sleep and fatigue. Rarer but dangerous forms include fluid in the lungs and swelling of the brain, both treated first by descending. Above 8,000 metres lies the so-called death zone, where no one can acclimatise fully and the body slowly deteriorates. Some populations have adapted over thousands of years: many Tibetans carry a variant of the gene EPAS1, inherited from the ancient Denisovans, that helps them avoid excess red blood cells, and Andean highlanders have their own set of adaptations. The highest permanent town, La Rinconada in Peru, sits at about 5,100 metres.

How we found out was dramatic. In 1875 the balloon Zénith rose above 8,000 metres over France, and two of its three aeronauts died of oxygen starvation. The French physiologist Paul Bert, who had advised them, showed in his 1878 book La Pression barométrique that the danger came from the low partial pressure of oxygen, not from low pressure as such.

Did you know? Reinhold Messner and Peter Habeler first climbed Everest without bottled oxygen in 1978, a feat many physiologists had thought impossible.

You meet thin air every time you fly. Airliner cabins are pressurised to the equivalent of roughly 1,800 to 2,400 metres, which is why your ears pop as the plane climbs and descends: the air trapped in the middle ear has to equalise through the narrow Eustachian tube. Altitude, in the end, is not a shortage of oxygen but a shortage of push.

Holding Your Breath

Take a deep breath and hold it, and within a minute or so most untrained adults find the urge to breathe irresistible. Surprisingly, it is not a lack of oxygen that forces you to give up. The main alarm is the rising level of carbon dioxide in the blood. Carbon dioxide dissolves to form acid, and central chemoreceptors, sensors on the surface of the brainstem, detect the resulting change in the acidity of the fluid around the brain. Smaller sensors in the neck, the carotid bodies, watch oxygen as well, but under normal conditions carbon dioxide is the trigger.

A breath-hold unfolds in stages. First the glottis closes and the diaphragm holds still. Carbon dioxide climbs steadily while oxygen falls more slowly. At the break point, typically after 30 to 90 seconds at rest, the drive to breathe becomes overwhelming. Those who push on feel the diaphragm begin to twitch in involuntary contractions, rhythmic spasms that trained freedivers learn to tolerate. With training, people stretch the hold dramatically, and elite freedivers have held their breath for more than eleven minutes on ordinary air while lying still in water.

Water helps. The mammalian dive reflex, triggered by cold water on the face, slows the heart, clamps down blood vessels in the arms and legs so that oxygen is saved for the heart and brain, and makes the spleen contract, squeezing extra red blood cells into circulation. The reflex is strongest in diving mammals such as seals, but it is clear in humans too.

The idea that breathing is driven by carbon dioxide was established by John Scott Haldane and John Gillies Priestley at Oxford, who showed in 1905 that the body adjusts breathing to keep carbon dioxide in the lungs remarkably constant. Their finding explains a real danger. Breathing fast and deep before a dive, hyperventilation, washes carbon dioxide out of the blood without adding much oxygen, so the urge to breathe arrives too late; oxygen can fall low enough to cause sudden loss of consciousness underwater with no warning, known as shallow-water blackout. On land, by contrast, you cannot hold your breath to the point of harm: if you passed out, the brainstem would simply restart breathing.

Did you know? The Bajau "sea nomads" of South-East Asia, who spend much of their working day freediving, have spleens about half as large again as those of their land-farming neighbours, an inherited adaptation.

Every swimmer who has pushed for one more length underwater has met the break point and felt the diaphragm protest. That burning urge is not your body running out of air. It is a carbon dioxide alarm, and it is almost always early.

Breathing During Exercise

At rest an adult breathes about six litres of air a minute. Start running and that figure climbs steeply, past 100 litres a minute in hard exercise and to 150 or more in elite endurance athletes. Each breath grows from about half a litre to as much as three, and the rate rises from 12 or so breaths a minute to 40 or more. Coordinating that change is a team effort, with the respiratory centre in the brainstem acting as conductor.

The first players are sensors. Breathing jumps within the first few seconds of exercise, before the blood's chemistry has had time to change. That early rise comes from the brain's own command to move, together with signals from mechanoreceptors in moving muscles and joints. As exercise continues, chemoreceptors in the brainstem and the carotid bodies fine-tune breathing to the rising output of carbon dioxide. The pumps respond: the diaphragm contracts harder and faster, while the intercostal and abdominal muscles join in to force air out rather than waiting for passive recoil. In the lungs, the airways widen slightly and capillaries that were idle at rest, especially at the tops of the lungs, open up, enlarging the surface for gas exchange.

Delivery matters as much as breathing. The heart's output rises from about 5 litres of blood a minute to 20 or 25 in a fit adult, and working muscles extract a much larger share of the oxygen passing through them, so blood returns to the heart far emptier. The body's oxygen use rises from about a quarter of a litre a minute at rest to its maximum, the VO2 max, typically 3 to 4 litres a minute in a healthy young adult and 5 or more in top endurance athletes. The British physiologist Archibald Vivian Hill measured runners' oxygen uptake in the 1920s and introduced the idea of a maximum oxygen intake, work that helped found exercise physiology.

As effort rises further, muscles produce lactic acid faster than it can be cleared. The blood buffers the acid with bicarbonate, releasing extra carbon dioxide, and breathing climbs out of proportion to the work. This ventilatory threshold is the point at which holding a conversation becomes hard, the basis of the simple talk test. In healthy people the lungs are rarely what limits performance; the heart and muscles usually give out first. But in exercise-induced bronchoconstriction, a form of asthma, the airways narrow during or after hard effort, often in cold, dry air.

Did you know? Training barely enlarges the lungs; what it builds is a stronger heart and muscles packed with more capillaries and mitochondria.

The panting after a sprint is the system catching up: repaying an oxygen debt, clearing carbon dioxide and lactate, and cooling the body. Breathlessness is not a failure of the lungs but a sign that the whole team is working.

Teeth and Chewing

Digestion begins with a bite. An adult mouth holds up to 32 permanent teeth, sixteen in each jaw, arranged in a horseshoe called the dental arch. At the front, eight chisel-edged incisors slice; beside them, four pointed canines grip and tear; behind them, eight premolars and twelve molars, including the four wisdom teeth, crush and grind on broad, cusped tops. Children manage with 20 milk teeth, which begin falling out at around six years old as the permanent set pushes up from below.

Every tooth has the same layered plan. The visible crown is capped with enamel, the hardest substance in the body, about 96 per cent mineral, mostly crystals of calcium phosphate called hydroxyapatite. Beneath it lies dentine, a yellowish, bone-like layer threaded with thousands of microscopic tubules. At the centre is the pulp, soft living tissue with blood vessels and nerves that enter through a tiny hole at the tip of each root. The roots sit in sockets in the jawbone, coated in a thin layer called cementum and slung in place by the periodontal ligament, a cushion of fibres that lets each tooth give very slightly under load.

Chewing, or mastication, is a precise piece of engineering. The masseter muscle, which you can feel bulge at the angle of your jaw when you clench, and its partner the temporalis pull the lower jaw up with a force of several hundred newtons at the molars. The jaw also slides sideways, so the molars grind as well as crush. The tongue and cheeks keep shuffling food back between the teeth, and saliva, between half a litre and a litre and a half a day, softens it into a moist ball. Saliva contains the enzyme amylase, which is why a piece of bread chewed for long enough begins to taste sweet: starch is already being split into sugar.

Did you know? Enamel contains no living cells, so unlike bone it can never repair itself; the cells that built it are lost as soon as the tooth breaks through the gum.

Teeth also reveal the oldest discovery in microbiology. In 1683 the Dutch lens-maker Antonie van Leeuwenhoek scraped the white matter from between his own teeth, looked at it through a microscope and described tiny moving "animalcules", the first recorded sighting of bacteria. Those same bacteria cause tooth decay: they ferment sugar into acid, and when the mouth turns acidic enough the enamel starts to dissolve. If a cavity reaches the dentine, the tubules carry hot, cold and sweet signals straight towards the nerve, which is why a damaged tooth twinges at ice cream.

Even healthy teeth feel cold for the same reason when gums recede and expose dentine at the neck. Behind every comfortable meal is a set of grinding tools built to last a lifetime from material that cannot be replaced.

Swallowing

Swallowing looks simple and is anything but. In under a second, food must cross the one place in the body where the routes for air and food meet, the pharynx or throat, without a crumb going the wrong way. Most adults swallow somewhere around 500 to 700 times a day, mostly saliva, and each time dozens of muscles in the tongue, palate, throat and neck fire in a strict order.

The first phase is voluntary. Once chewing has made a soft ball of food called a bolus, the tip of the tongue presses against the hard palate and rolls the bolus backwards, like toothpaste squeezed from a tube. When it touches the back of the mouth, sensors trigger the second phase, the pharyngeal reflex, and from here you are no longer in charge. The soft palate and the dangling uvula lift to seal off the nasal cavity, so food does not come out of your nose. The whole larynx, or voice box, jerks upwards and forwards (you can feel your Adam's apple rise), the vocal cords snap shut, breathing pauses, and the epiglottis, a leaf-shaped flap of cartilage, tips back over the entrance to the windpipe. The bolus slides over it into the oesophagus.

The third phase belongs to the oesophagus, the gullet, a muscular tube about 25 centimetres long running behind the windpipe and heart. It is closed at both ends by rings of muscle called sphincters. The upper one relaxes to let the bolus in; then a ring of contraction travels down the tube behind it, a wave called peristalsis, pushing it along at a few centimetres a second. A mouthful of solid food reaches the stomach in about 5 to 10 seconds, liquid rather sooner. Finally the lower oesophageal sphincter opens briefly and closes again to keep stomach acid where it belongs.

We first watched this in motion in 1896, months after X-rays were discovered, when the Harvard medical student Walter Cannon fed animals food laced with bismuth salts and followed it down the gullet on a fluoroscope screen. The same principle survives in the barium swallow used in hospitals today.

Did you know? Because peristalsis squeezes food along rather than letting it fall, you can swallow while standing on your head, and astronauts eat normally in orbit.

When the sequence fails, the consequences are serious. After a stroke the reflex can weaken, so food or drink slips into the airway, a problem called aspiration. If the lower sphincter relaxes when it should not, acid flows back up and burns, which is heartburn. And swallowing has a small bonus: the same muscles tug open the Eustachian tubes to the middle ears, which is why swallowing makes your ears pop on a descending plane.

The Stomach

The stomach is a muscular, J-shaped bag tucked under the left side of the diaphragm, between the end of the oesophagus and the start of the small intestine. Empty, it holds only a small cupful and its lining lies in deep folds called rugae. After a big meal those folds smooth out and it stretches to hold around 1 to 1.5 litres comfortably. Anatomists divide it into the cardia, where food enters, the domed fundus above, the large body, and the narrowing antrum that leads to the pylorus, a thick ring of muscle guarding the exit.

The stomach is less a digester than a blender and a sterilising tank. Its wall has three layers of muscle running lengthways, around and diagonally, an unusual extra layer that lets it squeeze, twist and churn. Several times a minute a wave sweeps towards the pylorus, mashing food against the closed exit and throwing it back, until it becomes a soupy paste called chyme. The pylorus then lets it out a few millilitres at a time, and a typical meal takes around two to four hours to leave.

Meanwhile, millions of pits in the lining pour out about 1.5 to 2 litres of gastric juice a day. Parietal cells pump out hydrochloric acid, bringing the contents to a pH between about 1.5 and 3.5, acid enough to kill most swallowed microbes. Chief cells release pepsinogen, which the acid converts into pepsin, an enzyme that starts chopping proteins. Parietal cells also make intrinsic factor, a protein without which vitamin B12 cannot be absorbed further down. The stomach avoids digesting itself by coating its lining in thick, alkaline mucus.

Did you know? The cells on the surface of the stomach lining live for only a few days before being shed and replaced, so you grow a fresh inner surface roughly twice a week.

Much of this was first seen through a hole. In 1822 a musket accident left the Canadian voyageur Alexis St Martin with a permanent opening into his stomach, and the US Army surgeon William Beaumont spent years dangling food into it on silk threads, timing digestion and sampling the juices. His book of 1833 showed that digestion is chemical, not just mechanical grinding.

When the mucus barrier fails, acid eats into the wall and causes a peptic ulcer. For decades ulcers were blamed on stress, until the Australians Robin Warren and Barry Marshall showed that most are caused by a bacterium, Helicobacter pylori. In 1984 Marshall drank a culture of it to prove the point, developed gastritis, and in 2005 the pair won the Nobel Prize. The everyday reminder of all this muscle is the rumble of an empty stomach: waves of contraction still sweeping through, pushing gas and fluid along with nothing to cushion the noise.

The Small Intestine

The small intestine is where food is actually taken into the body. It is "small" only in width, about 2.5 centimetres across, and enormous in length: around 6 metres when measured at post-mortem, and nearer 3 to 5 metres in a living person, whose muscles keep it bunched and toned. It coils through the middle of the abdomen, hung from the back wall on a fan-shaped sheet of tissue called the mesentery, which carries its blood vessels.

It has three parts. The duodenum, about 25 centimetres long, curls around the head of the pancreas and receives two crucial deliveries through a shared opening: bile from the liver and gallbladder, which breaks fat into tiny droplets, and pancreatic juice, which neutralises the stomach's acid and supplies enzymes for starch, protein and fat. Then come the jejunum, roughly two-fifths of the rest, where most absorption happens, and the ileum, the final three-fifths, which specialises in taking up vitamin B12 and recycling bile salts.

The secret of the small intestine is surface. Its lining rises in circular folds; the folds are covered in villi, finger-like projections about a millimetre tall; and the cells on each villus carry thousands of microscopic microvilli, a fuzz known as the brush border. Enzymes embedded in that brush border, such as lactase and sucrase, finish the job of breaking food into its smallest units. Sugars and amino acids then pass into a net of capillaries inside each villus and travel to the liver through the hepatic portal vein. Fats take a different route, entering a central lymph vessel called a lacteal and joining the bloodstream later. Food typically spends somewhere around two to six hours here.

Did you know? The cells lining the villi are among the fastest-renewed in the body: new ones are born in pits at the base, climb to the tip and are shed after only three to five days.

The often-quoted claim that the gut's inner surface would cover a tennis court is an overestimate. A careful study in 2014 put the whole digestive tract at about 30 square metres, roughly half a badminton court, most of it in the small intestine. It is still about fifteen times the area of your skin.

The duodenum also gave biology its first hormone. In 1902 the London physiologists William Bayliss and Ernest Starling found that acid entering a dog's duodenum released a chemical into the blood that made the pancreas secrete juice, even with its nerves cut. They called it secretin, and Starling later coined the word "hormone". When the lining is damaged, absorption suffers: in coeliac disease, the immune system reacts to gluten and flattens the villi. In most adults worldwide, lactase production falls after childhood, which is why milk gives so many people wind and cramps. The quiet tube in the middle of you is a vast and fast-renewing carpet.

The Liver

The liver is the largest internal organ and the body's chemical works. In an adult it weighs about 1.5 kilograms, a dark red-brown wedge filling the upper right of the abdomen beneath the ribs, with a large right lobe and a smaller left one. It is also unusual in its plumbing. About 1.5 litres of blood flow through it every minute, around a quarter of everything the heart pumps, and roughly three-quarters of that arrives not from an artery but from the hepatic portal vein, carrying everything just absorbed from the gut. The liver gets first look at every meal.

Inside, the tissue is organised into lobules, roughly hexagonal units about a millimetre across. Plates of liver cells, the hepatocytes, radiate from a central vein like the spokes of a wheel, with blood seeping past them through leaky channels called sinusoids. Each hepatocyte is a remarkably versatile worker. Textbooks list hundreds of separate jobs, but they fall into a few great trades.

The liver is a fuel store: after a meal it packs glucose away as glycogen, about 100 grams of it, and releases it again between meals. In 1857 the French physiologist Claude Bernard showed that the liver makes sugar itself, a discovery that helped found the idea of a stable internal environment. It is a factory, making albumin, the main protein of blood plasma, most of the clotting factors and cholesterol. It is a cleaner: it turns toxic ammonia from broken-down protein into urea for the kidneys to excrete, and breaks down alcohol and many drugs. It makes bile, roughly half a litre to a litre a day, which helps digest fat and carries away waste such as bilirubin, the yellow pigment left from worn-out red blood cells. And it is a larder and a guard, storing iron and vitamins A, D and B12, while specialised immune cells called Kupffer cells catch bacteria arriving from the gut.

Did you know? The liver can regrow to its full size from as little as a quarter of its original mass, which is what makes it possible for a living donor to give part of theirs.

The liver breaks down alcohol at a roughly fixed pace, which is why coffee, a cold shower or a brisk walk cannot sober anyone up; only time does. Repeated injury from alcohol, viral hepatitis or fat building up in the cells can leave the liver scarred and hardened, a state called cirrhosis, in which its many jobs begin to fail. When it cannot clear bilirubin, the pigment builds up and turns skin and the whites of the eyes yellow, which is jaundice. The same pigment, broken down in a bruise, explains why bruises turn yellow-green as they fade. Quietly, at about 1.5 kilograms, the liver is the busiest organ you never think about.

The Pancreas and Blood Sugar

The pancreas is a soft, pinkish gland about 15 centimetres long, lying across the back of the abdomen behind the stomach. Its broad head nestles in the C-shaped curve of the duodenum, and its body and tapering tail reach across to the spleen. It is really two organs in one. About 98 per cent of it is exocrine tissue, which makes around 1 to 1.5 litres of pancreatic juice a day, rich in bicarbonate to neutralise stomach acid and in enzymes that digest starch, fat and protein, delivered down a duct into the duodenum.

Scattered through it, like islands in a sea, are about a million tiny clusters of hormone-making cells, the islets of Langerhans, named after the German student Paul Langerhans, who described them in 1869 without knowing what they did. Together they make up only 1 or 2 per cent of the gland, but they control the body's fuel supply. Their beta cells make insulin; their alpha cells make glucagon.

Between them, these two hormones hold blood glucose in a narrow band, usually around 4 to 6 millimoles per litre when fasting, rising a little after meals. When you eat and sugar floods in from the gut, beta cells sense the rise and release insulin. Insulin acts like a key: it lets muscle and fat cells take glucose in, and tells the liver to stop releasing sugar and to store the excess as glycogen. As the level falls back, insulin release slows. Between meals or during exercise, when glucose dips, alpha cells release glucagon, which tells the liver to break glycogen down and pour glucose back into the blood. It is a classic negative feedback loop, working minute by minute without your noticing.

Did you know? All the glucose dissolved in an adult's blood at any one moment adds up to only about 4 or 5 grams, roughly a teaspoon of sugar.

When this loop breaks, the result is diabetes. In type 1 diabetes, the immune system destroys the beta cells, so almost no insulin is made; in type 2, much more common, the body's cells stop responding well to insulin and the beta cells cannot keep up. Before 1922, type 1 diabetes was a death sentence. Then in Toronto, Frederick Banting and Charles Best, working in John Macleod's laboratory, extracted insulin from the pancreas of dogs, and the biochemist James Collip purified it. In January 1922 a 14-year-old boy, Leonard Thompson, became the first person to be treated, and the following year Banting and Macleod shared the Nobel Prize.

The loop explains a familiar feeling: why you can skip lunch without collapsing. While your stomach complains, glucagon is quietly drawing on the liver's reserves to keep your brain supplied. A gland most people could not point to is balancing your fuel at every moment of the day.

The Large Intestine

The large intestine is shorter than the small intestine but much wider, about 1.5 metres long and up to 6 or 7 centimetres across. It forms a frame around the coiled small bowel. It begins low on the right at a blind pouch called the caecum, from which the worm-shaped appendix dangles, typically 8 to 10 centimetres long. From there the ascending colon climbs the right side of the abdomen, the transverse colon crosses beneath the stomach, the descending colon runs down the left, and the S-shaped sigmoid colon leads to the rectum and the anal canal. Three ribbons of muscle along its length, the taeniae coli, bunch the wall into a chain of pouches called haustra, which give the colon its puckered look.

By the time food reaches it, almost all the nutrients have gone. What arrives through the ileocaecal valve, roughly 1 to 1.5 litres a day, is mostly water, salts, fibre and dead cells. The colon's main task is to reclaim water and salt, so that only about 100 to 200 millilitres of water leave in the faeces. It works slowly. Contents usually take a day or two to pass through, churned back and forth by the haustra and then pushed onwards by a few strong mass movements a day. The colon is also the home of the gut's great crowd of bacteria, which ferment the leftover fibre and produce gas, the subject of the next chapter.

The final stage is controlled. When a mass movement fills the rectum, stretch sensors produce the urge to go. Two rings of muscle guard the exit: an inner sphincter that opens by reflex, and an outer one that you can tighten at will, which is why the urge can, within limits, be postponed. Faeces are about three-quarters water; much of the solid remainder is bacteria, living and dead, with undigested fibre and cells shed from the gut lining.

Did you know? The appendix, long dismissed as a useless leftover, is packed with immune tissue, and many researchers think it may serve as a safe store of gut bacteria for recolonising the colon after illness.

In the early 1970s the Irish surgeon Denis Burkitt compared stool weights and transit times in rural Africa and Britain, and argued that low-fibre Western diets were linked to constipation and bowel disease. The details are still debated, but his work put fibre on the map. When the colon goes wrong, waste may move too slowly, causing constipation, or too fast for water to be reclaimed, causing diarrhoea. In older people small pouches called diverticula can bulge through weak spots in the wall, and bowel cancer is common enough that many countries screen for it.

The colon's rhythm is familiar to anyone who has needed the toilet soon after breakfast. That is the gastrocolic reflex: food arriving in the stomach triggers a mass movement further down, making room for what is to come.

The Gut Microbiome

Your gut is home to trillions of microorganisms, together called the gut microbiome: mainly bacteria, along with archaea, fungi and viruses. A widely cited estimate from 2016 puts the total at about 38 trillion bacteria in an average adult, weighing around 200 grams, roughly the weight of an apple. A typical person carries a few hundred species, and every gut's mixture is a little different, like a fingerprint that changes with diet, age and medicine.

The crowd is far from evenly spread. The acid stomach holds very few microbes, perhaps a thousand per millilitre of contents. The numbers climb through the small intestine and explode in the slow, oxygen-free colon, where they reach something like 100 billion per gram, among the densest microbial communities on Earth. Most of them are anaerobes, organisms that cannot tolerate oxygen, which is one reason so many were overlooked until scientists began identifying them from their DNA.

They earn their keep. Our own enzymes cannot digest most dietary fibre, but gut bacteria can ferment it, releasing short-chain fatty acids such as butyrate, a main fuel for the cells lining the colon. Some bacteria make vitamin K and several B vitamins. The resident community trains the immune system from infancy, and it crowds out harmful newcomers simply by occupying the space and eating the food first. The by-products of fermentation include gases, mainly hydrogen, carbon dioxide and, in some people, methane, which is why a plate of beans has the effect it does.

Did you know? The old claim that bacteria outnumber your own cells ten to one was a rough guess from the 1970s; a careful count in 2016 put the ratio nearer one to one.

We found the first of these residents in 1885, when the German paediatrician Theodor Escherich isolated a bacterium from babies' nappies; it now bears his name, Escherichia coli. A baby's gut is colonised from birth onwards, from the mother, the surroundings and the first feeds, and the community becomes broadly adult-like within the first few years. Modern gene sequencing, scaled up by projects such as the Human Microbiome Project from 2007, revealed the full scale of the crowd.

Disturbing the community has consequences. A course of antibiotics can thin it out and let a harmful species, Clostridioides difficile, take over and cause severe diarrhoea. Remarkably, a faecal microbiota transplant, which restores a healthy community from a donor's stool, cures most such recurrent infections. Researchers are investigating links between the microbiome and conditions from obesity to inflammatory bowel disease, but many headlines run ahead of the evidence, and cause and effect are often unclear. What is certain is that you are never eating alone: every meal also feeds a guest list of trillions.

Metabolism: Burning Fuel

Metabolism is the sum of all the chemical reactions in the body. Some build things up, such as proteins from amino acids, which is anabolism; others break things down to release energy, which is catabolism. Food supplies the fuel, but cells cannot use a sandwich directly. They need a small, rechargeable energy carrier called adenosine triphosphate, or ATP. Splitting off one of its phosphate groups releases a packet of energy that powers muscle contraction, nerve signals and the building of new molecules. The body holds only a modest amount at any moment, so each molecule is recycled over and over; an adult turns over something close to their own body weight in ATP each day.

The main fuel route starts with glucose. In the watery cytoplasm of the cell, a ten-step sequence called glycolysis splits each six-carbon glucose into two molecules of pyruvate, netting two ATP. Pyruvate then enters the mitochondria, the cell's power stations, where it is converted to a two-carbon unit, acetyl coenzyme A. This feeds the Krebs cycle, a ring of reactions worked out by the German-born biochemist Hans Krebs in Sheffield in 1937, which strips the carbon atoms away as carbon dioxide and loads energetic electrons onto carrier molecules.

Those electrons are passed down the electron transport chain, a series of proteins in the mitochondrion's folded inner membrane. As they flow, they pump protons across the membrane, and the protons rush back through a tiny rotating motor, ATP synthase, which makes ATP. At the end of the line, the electrons combine with oxygen to form water. That is why you breathe: oxygen is the final catcher of electrons, and without it the chain stops. Fully burned, one glucose molecule yields around 30 to 32 ATP. Fats enter the same cycle after being chopped into two-carbon pieces, and yield about 9 kilocalories per gram against roughly 4 for carbohydrate or protein. Proteins can be burned too, once their nitrogen has been removed.

Did you know? When you lose fat, most of its mass leaves the body as carbon dioxide that you breathe out; the rest leaves as water.

The idea that living things burn their food is older than biochemistry. In the early 1780s Antoine Lavoisier and Pierre-Simon Laplace placed a guinea pig in an ice calorimeter, measured how much ice its body heat melted and compared that with the carbon dioxide it breathed out. Respiration, they concluded, is a slow combustion. At rest, an adult burns roughly 1,400 to 1,800 kilocalories a day just staying alive, and the brain, about 2 per cent of body weight, takes around a fifth of that. Most of the energy ends up as heat, which keeps you at 37°C, and when the machinery is faulty, as in inherited disorders such as phenylketonuria, a single blocked step can be serious. Every time you warm up on a run, you are feeling the furnace.

Vitamins and Minerals

Besides fuel and building material, the body needs a set of substances in tiny amounts, measured in milligrams or even micrograms a day. These micronutrients come in two groups. Vitamins are organic molecules that the body cannot make in sufficient quantities and must get from food; minerals are chemical elements, taken up from food and water, that form part of bones, blood and the machinery of cells.

There are 13 vitamins. Four are fat-soluble, A, D, E and K: they are absorbed with dietary fat and can be stored in the liver and fatty tissue, so a good stock lasts for months. Vitamin A makes the light-sensitive pigment in the retina; vitamin D controls the absorption of calcium; vitamin E protects cell membranes; vitamin K is needed to make clotting factors, and some of it is supplied by gut bacteria. The other nine are water-soluble: vitamin C and eight B vitamins, which mostly act as helpers for enzymes in metabolism. They are stored poorly, apart from B12, and any excess generally leaves in the urine, so they are needed regularly.

Minerals divide into the major minerals, needed in amounts of more than about 100 milligrams a day, and the trace elements. An adult body holds around a kilogram of calcium, 99 per cent of it in bones and teeth, alongside phosphorus, magnesium, and the sodium and potassium that carry every nerve impulse. Trace elements are needed in far smaller quantities but are just as essential: the 3 to 4 grams of iron in the body, mostly in haemoglobin, carry oxygen; iodine is built into thyroid hormones; zinc and selenium help hundreds of enzymes work.

The idea of a nutrient you could miss came slowly. In 1747 the Scottish naval surgeon James Lind gave different remedies to sailors with scurvy aboard HMS Salisbury, and those given oranges and lemons recovered fastest, one of the first controlled trials. The cause, a lack of vitamin C, which the body needs to make collagen, was only pinned down in the twentieth century. In 1912 the Polish biochemist Casimir Funk coined the word "vitamine", believing these factors were all "vital amines". They are not, so the final "e" was later dropped.

Did you know? A polar bear's liver holds so much vitamin A that eating even a small portion can poison a person, a danger Arctic explorers discovered the hard way.

Deficiencies produce classic diseases: too little vitamin D and calcium softens growing bones in rickets, too little iron causes anaemia, and too little iodine swells the thyroid into a goitre. Excess can also harm, especially with fat-soluble vitamins, which accumulate. Your skin makes vitamin D from sunlight, which is why levels tend to drop in a northern winter. British sailors were nicknamed "limeys" for the citrus juice that kept scurvy away, a reminder that the smallest part of a diet can decide the fate of a voyage.

The Brain

The brain is a soft, pinkish-grey organ weighing about 1.3 to 1.4 kilograms in an adult, roughly 2 per cent of body weight, with the texture of firm tofu. It floats in about 150 millilitres of cerebrospinal fluid, the clear liquid that cushions it, so that inside the skull it effectively weighs only a few dozen grams. Most of what you see is the cerebrum, split into left and right hemispheres joined by the corpus callosum, a bridge of some 200 million nerve fibres. Tucked underneath at the back sits the cerebellum, or "little brain", and below everything the brainstem tapers down into the spinal cord.

The outer layer of the cerebrum, the cerebral cortex, is only 2 to 4 millimetres thick but heavily folded into ridges (gyri) and grooves (sulci); spread flat it would cover roughly a quarter of a square metre. Deep grooves divide each hemisphere into four lobes. The frontal lobe plans, decides and sends commands to the muscles; the parietal lobe handles touch and the sense of where things are; the temporal lobe processes hearing, language and memory; and the occipital lobe, at the back, is devoted to vision. The cerebellum fine-tunes movement and balance, while the brainstem keeps breathing, heart rate and swallowing running without a moment's thought.

The numbers are startling. The brain contains about 86 billion neurons and a comparable number of support cells called glia. Remarkably, around 69 billion of those neurons are packed into the cerebellum, which makes up only a tenth of the brain's volume. Running all this costs about 20 per cent of the body's resting energy, roughly the power of a dim 20-watt bulb, supplied by about 750 millilitres of blood a minute.

How we found out owed much to injury. In 1861 the French surgeon Paul Broca examined a patient who could say only one syllable, "tan"; after the man died, Broca found damage in the left frontal lobe, the first convincing proof that particular abilities live in particular places. Today scanners show the same lesson in reverse, and they also bury a stubborn myth: we do not use only 10 per cent of our brains. Over a day, virtually every region is active.

Did you know? The brain has no pain receptors of its own, so surgeons can operate on some patients while they are awake and talking, mapping speech areas as they go.

When the blood supply fails, the damage is swift. In a major stroke, caused by a blocked or burst artery, an estimated 1.9 million neurons can die every minute without treatment, which is why speed matters so much. A headache, oddly, is not the brain hurting at all but the membranes and blood vessels around it. Three pounds of folded tissue, and everything you have ever thought happened inside it.

Neurons

A neuron is a nerve cell, built to carry information as an electrical signal. Most share the same basic plan. Branching dendrites, like the roots of a tree, collect incoming messages. They feed into the cell body, or soma, which holds the nucleus and is usually between 4 and 100 micrometres across. From the cell body a single long fibre, the axon, carries the signal away, ending in a spray of terminals that pass it on to other cells. The axon can be astonishingly long: a motor neuron controlling the big toe has its cell body in the lower spinal cord and an axon reaching about a metre down the leg.

The signal itself is the action potential. At rest the inside of a neuron is about 70 millivolts negative compared with the outside, a charge kept up by pumps that push sodium ions out and potassium ions in. When enough input pushes the membrane up to a threshold of roughly minus 55 millivolts, channels snap open and sodium floods in, flipping the inside briefly positive. Potassium channels then open to reset it. The whole spike lasts about a millisecond and is all-or-nothing: a neuron does not fire harder for a stronger stimulus, it fires more often, up to several hundred times a second.

Speed depends on insulation. Many axons are wrapped in myelin, a fatty sheath laid down by glial cells, with tiny gaps called nodes of Ranvier. The signal leaps from node to node, so a thick myelinated fibre can conduct at up to about 120 metres a second, while thin bare fibres manage barely 1 metre a second. That difference is why you feel the sharp first touch of a stubbed toe before the slow, dull ache arrives.

We owe the picture to two rivals. Using a silver stain invented by Camillo Golgi, the Spanish anatomist Santiago Ramón y Cajal drew thousands of neurons in the 1880s and 1890s and argued that each is a separate cell, not part of a continuous net as Golgi believed. They shared the Nobel Prize in 1906 and disagreed in their lectures. In 1952 Alan Hodgkin and Andrew Huxley worked out the action potential using the giant axon of a squid, about half a millimetre wide.

Did you know? When your leg "goes to sleep", pressure has squeezed the nerve and its blood supply; the pins and needles are neurons misfiring as they recover.

When myelin is attacked, as in multiple sclerosis, signals slow, scatter or fail, producing numbness, weakness or blurred vision depending on where the damage lies. Each neuron makes thousands of connections, and in the end it is these humble electrical flickers that become every sight, word and decision.

Synapses and Neurotransmitters

Neurons almost never touch. Where one passes a message to the next there is a synapse: the swollen tip of an axon, a gap called the synaptic cleft only about 20 to 40 nanometres wide, and the receiving membrane of the next cell on the other side. Inside the tip wait hundreds of tiny bubbles, or vesicles, each loaded with thousands of molecules of a chemical messenger, a neurotransmitter. The human brain contains something like 100 trillion synapses, far more than there are stars in the Milky Way.

The handover takes well under a millisecond. When an action potential reaches the axon tip, it opens channels that let calcium ions rush in. The calcium makes vesicles fuse with the membrane and spill their contents into the cleft. The transmitter drifts across and docks with receptors on the far side, like keys in locks, opening ion channels there. Some transmitters make the receiving cell more likely to fire; others make it less likely. The signal must then be switched off, so the transmitter is quickly pumped back into the axon (reuptake), broken down by enzymes, or simply diffuses away.

The brain's main accelerator is glutamate and its main brake is GABA; between them they carry most fast signals. Acetylcholine tells skeletal muscles to contract. Dopamine helps to drive movement, motivation and learning from reward, while serotonin and noradrenaline tune mood, attention and arousal. Strikingly, about 90 per cent of the body's serotonin is made not in the brain but in the gut.

The chemical idea came from a dream. In 1921 the German pharmacologist Otto Loewi, by his own account, woke at night with an experiment in mind: he stimulated the vagus nerve of one frog heart, slowing it, then bathed a second heart in the fluid, and it slowed too. Some substance, which he called Vagusstoff and which proved to be acetylcholine, had carried the message. He shared the 1936 Nobel Prize with Henry Dale.

Did you know? Loewi first dreamed the experiment, scribbled it down and could not read his notes in the morning; the dream returned the next night, and this time he went straight to the laboratory.

Because synapses are where signals can be turned up or down, they are where much goes wrong. In Parkinson's disease, dopamine-making neurons in the midbrain die, causing tremor and slowness. In myasthenia gravis, the immune system attacks acetylcholine receptors on muscles, causing weakness. Many toxins work here too: botulinum toxin stops acetylcholine release, and nerve agents stop it being cleared. Even your morning coffee acts at synapses, blocking receptors for adenosine, a molecule that builds up while you are awake and makes you feel drowsy. Thought, at bottom, is a conversation in chemicals.

The Spinal Cord and Reflexes

The spinal cord is the main cable linking the brain to the body. It runs from the base of the skull down a tunnel formed by the vertebrae, and it is surprisingly modest: about 45 centimetres long, roughly as thick as a finger, and weighing only around 35 grams. It stops short at the level of the first or second lumbar vertebra, in the small of the back; below that a bundle of nerve roots continues down like a horse's tail, the cauda equina. Along its length, 31 pairs of spinal nerves branch off through gaps between the vertebrae to the skin, muscles and organs.

Cut across, the cord shows a butterfly of grey matter, made of nerve cell bodies, surrounded by white matter, bundles of myelinated axons running up and down like lanes of a motorway. Each spinal nerve joins the cord by two roots. The dorsal root, at the back, brings sensory signals in, and its swelling, the dorsal root ganglion, holds the cell bodies of the sensory neurons. The ventral root, at the front, carries motor commands out from cells in the front horns of the butterfly.

The cord is not just a cable; it can act on its own. A reflex is an automatic response wired through it. When a doctor taps the tendon below your kneecap, the thigh muscle is stretched a little. Stretch sensors called muscle spindles fire; the sensory neuron carries the signal into the cord and connects directly with a motor neuron, which makes the same muscle contract and the leg kick. At the same time a small connecting neuron relaxes the hamstrings at the back of the thigh so they do not fight it. With just one synapse in the main loop, the kick follows the tap within a few hundredths of a second. The British physiologist Charles Sherrington mapped such reflexes around 1900 and coined the word "synapse".

Did you know? At birth the spinal cord reaches about the third lumbar vertebra, but the bony spine keeps growing longer than the cord, so in adults it ends near the first.

The withdrawal reflex is cleverer still. Touch a hot pan and your hand jerks back before the brain has registered pain, while the opposite leg stiffens to keep you upright. Messages to the brain arrive a moment later, which is why the "ouch" comes after the movement.

Because so much traffic passes through it, damage to the cord is serious. An injury cuts off everything below the level of the damage: in the lower back it can paralyse the legs, while in the neck it can affect all four limbs and even breathing. Doctors test reflexes because they reveal which segments are working. A tap of a rubber hammer, and a 45-centimetre cable shows what it can do without asking permission.

The Autonomic Nervous System

Most of what keeps you alive happens without your permission. The autonomic nervous system is the part of the nervous system that runs the organs automatically: heart rate, blood pressure, breathing rhythm, digestion, sweating, the size of the pupils and the emptying of the bladder. Its commanders sit in the hypothalamus and the brainstem, and its nerves reach the heart, the smooth muscle in blood vessels and gut walls, and the glands.

It has two main branches that usually pull in opposite directions. The sympathetic nervous system prepares the body for action, the famous "fight or flight" named by the American physiologist Walter Cannon in 1915. Its nerves leave the spinal cord between the chest and the upper lower back and pass through a chain of relay stations, the sympathetic ganglia, lying like beads on either side of the spine. Their endings mostly release noradrenaline. Switched on, it widens the pupils and airways, speeds the heart, sends blood to the muscles, slows digestion and releases glucose. It also prompts the adrenal glands to pour adrenaline into the blood, a story told in its own chapter.

The parasympathetic nervous system is the "rest and digest" branch. Its fibres leave from the brainstem and the base of the spine, and its endings release acetylcholine. Its star is the vagus nerve, the "wandering" nerve, which carries roughly three-quarters of all parasympathetic fibres from the brainstem down to the heart, lungs and gut. It slows the heart, narrows the pupils, stimulates saliva and stomach acid and gets the intestines moving. A third division, the enteric nervous system, is a mesh of some 400 to 600 million neurons in the gut wall that can run digestion largely on its own.

The two branches are less an on-off switch than a pair of dials. The heart's own pacemaker would beat about 100 times a minute if left alone; at rest the vagus applies a constant brake that holds it nearer 60 to 70. The British physiologist John Newport Langley named the system "autonomic" around 1898 after tracing its relay stations with nicotine.

Did you know? A transplanted heart has had its nerves cut, so with no vagal brake it typically beats faster at rest, often around 90 to 110 times a minute.

You meet both branches daily. Before a speech, your mouth goes dry and your heart pounds as the sympathetic side takes over; after a big meal you feel sluggish as the parasympathetic side settles in. Goosebumps come from sympathetic nerves tightening tiny muscles at the base of each hair. Things go wrong when the balance tips: a sudden surge of vagal activity can drop the heart rate and blood pressure and cause a faint. Two quiet branches, working day and night, so that you never have to remember to digest.

Memory

Memory is not one thing kept in one place. It is a family of abilities, each with its own timescale and its own parts of the brain. The first stage is sensory memory, a brief echo of what you have just seen or heard that fades in under a second, or a few seconds for sound. What you pay attention to passes into working memory, the mental scratchpad you use to hold a phone number while you dial it. It is small, holding roughly four items at once, and without rehearsal its contents vanish in 20 to 30 seconds.

Anything kept longer becomes long-term memory, whose capacity has no known limit. It comes in two broad kinds. Explicit memories are those you can bring to mind and put into words: episodic memories of events in your own life, such as your last birthday, and semantic memories of facts, such as the capital of France. Implicit memories show themselves in what you do rather than what you can say, above all procedural memory for skills like riding a bicycle or typing.

Forming an explicit memory has three steps. Encoding turns an experience into a pattern of activity across the cortex. Consolidation then stabilises it over hours to years, a process steered by the hippocampus, a curled structure about 4 centimetres long inside each temporal lobe whose name means "seahorse". Much consolidation happens during sleep. Finally, retrieval brings the memory back. Crucially, recall is reconstruction, not replay: each time you remember an event you rebuild it, and details can shift, which is why confident eyewitnesses can be wrong.

The most famous patient in neuroscience showed how the system divides. In 1953 Henry Molaison, known for decades as H.M., had most of both hippocampi removed to stop severe epilepsy. Afterwards he could hold a conversation and remember his childhood, but he could no longer form new explicit memories; people he met were strangers again minutes later. The psychologist Brenda Milner showed that he could still learn new skills.

Did you know? H.M. got steadily better at tracing a star while watching only its mirror image, yet each day he insisted he had never tried the task before.

Skills, by contrast, depend mainly on the basal ganglia and the cerebellum, which is why they survive damage that wipes out events. In Alzheimer's disease the hippocampus is among the first regions hit, so new memories fail first while old ones linger. Forgetting itself is normal and useful: in 1885 Hermann Ebbinghaus, memorising nonsense syllables, showed that most new information fades within a day unless revisited. Walking into a room and forgetting why is the system working as designed, keeping what matters and quietly discarding the rest.

Learning and Plasticity

Every time you learn something, your brain physically changes. This capacity to rewire is called neuroplasticity, and it works mainly at the synapses, the junctions between neurons. In 1949 the Canadian psychologist Donald Hebb proposed that when one neuron repeatedly helps to fire another, the connection between them grows stronger. The idea is often summed up as "neurons that fire together wire together", and it has held up remarkably well.

The mechanism was caught in action in 1973, when Tim Bliss and Terje Lømo stimulated a pathway in the rabbit hippocampus with rapid bursts and found the connection stayed strengthened for hours, later shown to last days or more. This long-term potentiation depends on a special receptor, the NMDA receptor, which opens only when the sending cell releases glutamate and the receiving cell is already active. The resulting calcium inflow triggers the receiving cell to add more receptors, and over days the tiny dendritic spines that hold synapses grow, split or sprout anew. Connections that fall out of use weaken and are removed. Learning is the sculpting of this wiring.

Plasticity is greatest in childhood. A newborn's cortical neurons each carry perhaps 2,500 synapses; by the age of two or three the figure is often cited at around 15,000, far more than an adult keeps. Through later childhood and adolescence the brain prunes the unused connections, while insulating myelin is added, the frontal lobes last of all, into the mid-twenties. There are also critical periods when certain wiring must be shaped by experience. In the 1960s David Hubel and Torsten Wiesel showed that if one eye of a kitten was kept closed early in life, the visual cortex was rewired to favour the other eye for good, work that earned them a share of the 1981 Nobel Prize.

Did you know? London taxi drivers, who spend years memorising some 25,000 streets, were found in a 2000 study to have a larger rear part of the hippocampus than comparable people.

Adult brains remain plastic, just less dramatically. People learning to juggle show measurable changes in grey matter in motion-sensing areas within months. After a stroke, neighbouring regions can take over some lost functions, which is the basis of rehabilitation. Whether adults grow many new neurons in the hippocampus is still debated among scientists. When plasticity misfires, as in a child with an untreated lazy eye, the brain can learn to ignore an input, and the window for full correction narrows with age.

The everyday lessons follow from the biology: spaced practice beats cramming, because each session reactivates and strengthens the same connections; sleep helps to lock in what you learned; and challenge matters more than repetition alone. The brain you have tomorrow depends a little on what you do today.

Emotions

An emotion is more than a feeling. Fear, for instance, has three parts working together: a rapid judgement that something matters, a surge of bodily changes, and the conscious experience you call being afraid. Which comes first has been argued for well over a century. In 1884 the American psychologist William James suggested that we do not tremble because we are afraid but feel afraid because we tremble. Walter Cannon objected that the body reacts too slowly and too uniformly for that. Today most researchers see a loop in which body and brain constantly inform each other.

The brain regions involved were once grouped as the limbic system, a ring of structures around the brainstem. Its key member is the amygdala, an almond-shaped cluster of neurons about 1.5 centimetres long deep in each temporal lobe. It acts as a threat detector, receiving a quick, rough copy of sensory signals straight from the thalamus, the brain's relay station, so it can trigger alarm before the cortex has worked out what you are looking at. That is why you can leap back from a coiled hosepipe before you realise it is not a snake.

The amygdala then calls in the hypothalamus, which drives the autonomic nervous system and the stress hormones: the pounding heart, the dry mouth, the butterflies as blood is diverted from the gut. The hippocampus next door attaches the emotion to a memory of the place and time, which is why strongly emotional events are remembered so vividly. The insula, a fold of cortex tucked deep inside, reads the state of the body and is especially active in disgust. Finally the prefrontal cortex, behind the forehead, can rein all this in, reinterpreting a situation so that a racing heart becomes excitement instead of dread.

How much emotions are universal is still debated. In 1872 Charles Darwin argued in The Expression of the Emotions in Man and Animals that facial expressions are inherited, and later work by Paul Ekman suggested six basic expressions are recognised across cultures: happiness, sadness, fear, anger, surprise and disgust. Others argue that emotions are built from more basic ingredients by each brain and culture.

Did you know? A genuine smile involves a muscle around the eyes that most people cannot contract at will; the French neurologist Guillaume Duchenne described this in 1862, and it still bears his name.

Patients show how the parts divide. A woman known as S.M., whose amygdalae were destroyed by a rare disease, has been studied for decades because she seems unable to feel fear, approaching snakes and spiders with curiosity. When the emotional circuitry is overactive or stuck, the result can be anxiety disorders or depression. A blush, a lump in the throat, a jolt of fright on the stairs: each is this team acting together, faster than words.

Sleep

Sleep is not the brain switching off but switching modes. Through a typical night an adult passes through four to six sleep cycles, each lasting roughly 90 minutes, moving down through lighter and deeper stages and back up into dreaming. Recordings of the brain's electrical activity, the electroencephalogram or EEG, pioneered by the German psychiatrist Hans Berger in the 1920s, reveal the stages as different rhythms of brain waves.

Drifting off, you enter stage N1, a few minutes of light sleep in which the muscles relax and you may feel the sudden jolt of a hypnic jerk. Stage N2 follows, marked by bursts of activity called sleep spindles; it fills about half of the night. Then comes stage N3, or slow-wave sleep, when large, slow delta waves sweep the cortex, breathing and heart rate drop, and growth hormone is released. This is the deepest sleep, hardest to wake from, and it is concentrated in the first half of the night. Finally comes REM sleep, named after the rapid eye movements that accompany it. The brain becomes almost as active as when awake and most vivid dreams occur, yet the muscles of the limbs are actively paralysed. REM periods lengthen towards morning and make up about a fifth to a quarter of the night.

REM sleep was discovered in 1953 at the University of Chicago, when the graduate student Eugene Aserinsky and his supervisor Nathaniel Kleitman noticed the darting eye movements of sleeping volunteers, including Aserinsky's own young son. Since then we have learned that sleep does real work. It helps consolidate memories, replaying the day's experiences in the hippocampus and cortex. Studies in mice suggest that during deep sleep the fluid-filled spaces around brain cells widen and waste products are flushed out more efficiently.

The urge to sleep builds through the day as a molecule called adenosine accumulates in the brain, combining with the body clock that times when you feel sleepy. Most adults need about 7 to 9 hours. In 1964 a 17-year-old Californian, Randy Gardner, stayed awake for about 264 hours, roughly 11 days, and by the end struggled with speech, memory and mood.

Did you know? During REM sleep only your eyes and breathing muscles escape the paralysis; waking briefly while it lingers causes sleep paralysis, the frightening sense of being unable to move.

When the system breaks, the effects are clear. In sleep apnoea the throat repeatedly collapses and breathing stops; in narcolepsy, loss of neurons that make the wakefulness chemical orexin lets REM sleep intrude into the day. Sleepwalking happens in deep N3 sleep, not in dreams. Every night, without any effort on your part, the brain dims the lights and gets on with its housekeeping.

Consciousness

Consciousness is the one thing everyone experiences and no one has fully explained. Doctors and neuroscientists find it useful to separate two aspects. The first is level, or wakefulness: whether the eyes are open and the brain is aroused. This depends on a network in the brainstem called the reticular activating system, which projects up through the thalamus, the brain's central relay, to the cortex. The second is content, or awareness: what you are actually experiencing, which depends on rich two-way traffic between the thalamus and wide areas of the cortex.

Plotting the two against each other maps the states of the mind. Normal waking life sits high on both. In deep sleep and general anaesthesia both fall together. In REM sleep arousal is low but awareness, in the form of dreams, returns. In a coma both are absent: the eyes stay closed and the person cannot be woken. Most unsettling is the vegetative state, now often called unresponsive wakefulness, in which a person opens their eyes and has sleep-wake cycles yet shows no sign of awareness. Doctors grade responsiveness on the Glasgow Coma Scale, introduced in 1974, which scores eye, verbal and movement responses from 3 to 15.

Such categories are not always what they seem. In 2006 a team led by the British neuroscientist Adrian Owen asked a young woman in an apparent vegetative state, lying in a brain scanner, to imagine playing tennis. A movement-planning area of her brain lit up, exactly as in healthy volunteers, suggesting she understood. In locked-in syndrome, damage to the brainstem paralyses almost the whole body while leaving awareness intact.

Did you know? The French editor Jean-Dominique Bauby, locked in after a stroke in 1995, wrote the memoir The Diving Bell and the Butterfly by blinking his left eyelid as an assistant recited the alphabet.

Experiments show how much happens outside awareness. In split-brain patients, whose corpus callosum had been cut to treat epilepsy, Roger Sperry and Michael Gazzaniga found in the 1960s that each hemisphere could know things the other did not. In a famous 1999 study, about half of viewers counting basketball passes failed to notice a person in a gorilla suit walking through the scene. And when you drive a familiar route and arrive with no memory of the journey, your brain has handled the road while your awareness was elsewhere.

How electrical activity becomes experience remains open. Some theories propose that information becomes conscious when it is broadcast across a "global workspace" of the brain; others tie it to how tightly information is integrated. The philosopher David Chalmers called this the "hard problem". Whatever the answer, it is being worked on, fittingly, by the very thing it is trying to explain.

The Eye

The eyeball is a slightly squashed sphere about 24 millimetres across, weighing roughly 7 grams, cushioned in fat inside the bony socket of the skull and steered by six small muscles. Its tough white outer coat is the sclera; at the front this becomes the cornea, a clear dome about half a millimetre thick with no blood vessels at all. Behind the cornea lies the coloured iris, a ring of muscle around a hole, the pupil, and behind that the lens. A clear jelly called the vitreous humour fills the large chamber at the back, and lining its rear wall is the retina, the thin sheet of light-sensitive tissue that does the actual seeing.

Light travels through the eye in a strict order. The curved cornea does about two-thirds of the bending needed to focus. The iris adjusts the pupil from about 2 to 8 millimetres across, like the aperture of a camera. The lens then fine-tunes the focus by changing shape: for near objects a ring of ciliary muscle contracts, the fibres holding the lens slacken, and the lens bulges rounder. The result is a sharp, small and upside-down image on the retina, which the brain turns the right way up without being asked.

The retina is only about a quarter of a millimetre thick, yet it holds around 120 million rods, which work in dim light but see no colour, and about 6 million cones, which handle colour and fine detail. The cones crowd into the fovea, a pit about 1.5 millimetres wide at the centre of gaze; this is why you point your eyes at whatever you want to read. Oddly, the retina is wired back to front, so light passes through layers of nerve cells before reaching the receptors. Their output gathers into roughly a million fibres that leave through the optic nerve, creating a blind spot with no receptors at all. You never notice it, because the brain fills the gap.

Did you know? Your blind spot is wide enough to hide around ten full moons placed side by side, yet the brain papers over it so well that most people never find it.

How we found out took a leap of imagination. In 1604 Johannes Kepler argued that the eye forms an inverted image on the retina, and Christoph Scheiner soon confirmed it by peeling back the outer coats of an animal's eye and watching an upside-down scene appear.

When the optics go wrong, the image lands in the wrong place. In short sight the eyeball is too long and focus falls in front of the retina; in long sight it falls behind. From the mid-forties the lens stiffens, which is why menus drift to arm's length, and a cataract clouds it. Every glance is a small feat of engineering.