How does
life work?

Hippocrates and his school tried to explain disease by natural causes rather than divine punishment. Humoral theory, which held that the body is made of four humors, blood, phlegm, yellow bile and black bile, and that illness comes when their balance is upset, remained the basic framework of medicine until the 19th century.

• Hippocrates ↗

In physics Aristotle left theories that were wrong for 2,000 years, but in biology he was a true observer. Dissecting and observing on the island of Lesbos, he described and classified more than 500 species, and knew that dolphins are not fish but bear live young and nurse them. He set living things in a single line from simple to complex, the "ladder of nature," but he also supported spontaneous generation, the idea that life arises on its own from mud.

• Aristotle's biology ↗

Aristotle's student Theophrastus described hundreds of plants by form, reproduction and use, laying the foundations of botany.

The Roman physician Galen treated gladiators, dissected monkeys and pigs, and built a vast medical system. He showed by experiment that nerves move muscles and that arteries carry blood, not air. But since he could not dissect humans, he applied animal anatomy directly to people, and made many errors. His position resembles Ptolemy's in astronomy.

• Galen ↗

Ibn Sina (Avicenna) wrote The Canon of Medicine, gathering Greek and Islamic medical knowledge into one work. Translated into Latin, it was the standard medical textbook in European universities until the 17th century.

• The Canon of Medicine ↗

Ibn al-Nafis was the first to describe pulmonary circulation, blood traveling from the right side of the heart through the lungs to the left. He rejected Galen's claim of invisible pores in the heart's wall. His work remained almost unknown in Europe.

Mondino of the University of Bologna wrote an anatomy textbook based on public human dissections. For a long time afterward, though, anatomy lessons consisted of a professor reading Galen aloud from a high chair while an assistant wielded the knife, so there were few new discoveries.

Vesalius published the results of his own dissections with precise engravings and pointed out more than 200 of Galen's errors. Appearing in the same year as Copernicus's book, it has led some to date the start of the Scientific Revolution to 1543. The precision of the engravings owed a debt to the perspective and anatomical studies of Renaissance art.

• De Humani Corporis Fabrica Libri Septem ↗

Harvey multiplied the amount of blood the heart pumps with each beat by the number of beats and showed that in an hour it pushes out more blood than a person weighs. The liver could not keep making that much blood, so the same blood must be going around. It was one of the first times a biological problem was solved by calculation. He could not, however, show how blood passed from arteries to veins.

• William Harvey ↗

Looking at a frog's lung under the microscope, Malpighi discovered the tiny capillaries connecting arteries and veins. The theory of circulation was finally complete.

Robert Hooke made precise drawings of what he saw under the microscope, from a flea and a fly's eye to cork. He compared the tiny compartments in cork to monks' small rooms and called them "cells," the origin of the word. He is the same Hooke who quarreled with Newton over the inverse-square law.

• Micrographia ↗

Redi showed that maggots do not appear in jars of meat whose mouths are covered with cloth. It was the first experimental challenge to spontaneous generation, though the belief survived that invisible microbes, at least, arise on their own.

Using lenses he made himself, Leeuwenhoek, a Dutch draper, was the first to observe bacteria, protists, sperm and red blood cells. An amateur opened up an entire invisible world of life.

• Antonie van Leeuwenhoek ↗

Linnaeus classified living things in a hierarchy of kingdom, class, order, genus and species, and established binomial nomenclature, naming each species with a genus and a species name. He also coined Homo sapiens. Linnaeus did for biology what Lavoisier's nomenclature did for chemistry. Yet he believed species remained exactly as God created them.

• Systema Naturae ↗
• Binomial nomenclature ↗

In his vast Natural History, Buffon argued that the Earth is much older than the 6,000 years calculated from the Bible, and cautiously hinted that species could change.

Preformation, which held that a tiny person already exists inside the sperm or egg, clashed with epigenesis, which held that the embryo forms step by step. Observing chick embryos, Wolff supported epigenesis: organs are not there from the start but form gradually.

Spallanzani showed that no microbes appear in broth that is boiled for a long time and then sealed. Opponents countered that boiling destroys a "vital force" in the air, and the debate continued for a hundred years until Pasteur.

Galvani found that a dead frog's leg convulses when touched by two different metals and called it "animal electricity." In refuting him, Volta invented the battery in 1800. The voltaic pile, which transformed physics and chemistry, came out of a biology experiment. It was also the starting point of the idea that nerves and muscles run on electricity.

• Luigi Galvani ↗

Jenner showed that inoculating people with cowpox, a mild disease of cattle, protected them against deadly smallpox. The word "vaccine" comes from vacca, Latin for cow. In 1980 smallpox became the first disease humanity eradicated.

• Edward Jenner ↗
• Smallpox vaccine ↗

In his Zoological Philosophy, Lamarck put forward the first systematic theory of evolution: organs that are used heavily develop, and the traits so acquired are passed to offspring. His mechanism was wrong, but his core idea, that species change, was right.

• Lamarckism ↗

Cuvier established comparative anatomy and, studying fossils such as mammoths, proved that extinction really happens. Before then, it was assumed that species created by God could not vanish. But he argued for catastrophism, repeated upheavals that wiped out living things, and rejected evolution.

Lyell argued for uniformitarianism: slow processes still at work today, such as erosion and deposition, accumulate over immense time to shape the land. This idea of a vastly old Earth deeply influenced Darwin, who carried the book aboard the Beagle.

• Principles of Geology ↗

Sailing the world for five years on HMS Beagle, Darwin saw fossils of giant extinct animals in South America and, in the Galápagos, finches and tortoises that differed slightly from island to island. Analyzing his specimens back home, he became convinced that species change, and in 1838, reading Malthus's Essay on the Principle of Population, he hit upon the core idea of natural selection. Fearing the backlash, he held off publishing for 20 years while gathering evidence.

• Second voyage of HMS Beagle ↗

Schleiden showed that all plants are made of cells, and the next year Schwann showed the same for animals. That plants and animals are built from the same basic unit became a unifying principle of biology.

• Cell theory ↗

Semmelweis concluded that doctors examining mothers with hands fresh from dissecting corpses were causing childbed fever, and by having them wash in chlorine solution he sharply cut the death rate. But with germ theory not yet established, colleagues ridiculed him, and he died in an asylum.

Virchow established that new cells arise only from the division of existing cells, ruling out spontaneous generation even at the level of the cell. He founded cellular pathology, which explains disease as abnormalities of cells.

Alfred Russel Wallace, working in the Malay Archipelago, sent Darwin a letter laying out almost exactly the same theory of natural selection. Arranged by colleagues, papers by both men were presented together at the Linnean Society.

• Alfred Russel Wallace ↗

Organisms produce more offspring than can survive, and offspring vary, so individuals with variations even slightly better suited to their environment survive and reproduce more. Darwin hurried On the Origin of Species into print, and it became the framework that unified all of biology. But he did not know how heredity worked.

• On the Origin of Species ↗
• Natural selection ↗

At a debate in Oxford, "Darwin's bulldog" Thomas Huxley famously faced off against Bishop Wilberforce. It became an emblem of the clash between science and religion over evolution.

Pasteur boiled broth in flasks with S-shaped necks. Air could get in, but dust and microbes caught in the curved neck, and the broth never spoiled. He also showed that fermentation is the work of microbes, and invented pasteurization, heating wine and milk to kill microbes.

• Louis Pasteur ↗
• Spontaneous generation ↗

In his monastery garden, the friar Gregor Mendel crossed pea plants, tracked traits such as flower color and seed shape one at a time, and counted the offspring. He found that traits do not blend but pass on as separate units, appearing in fixed ratios such as 3:1 and 9:3:3:1. It was exactly the answer to Darwin's problem, but it was almost completely ignored for 34 years.

• Gregor Mendel ↗
• Mendelian inheritance ↗

Claude Bernard introduced the idea of the "internal environment": living things keep conditions inside the body constant even as the outside world changes. It later became the concept of homeostasis. He made physiology a rigorous experimental science.

Haeckel named the study of the relationships between organisms and their environment "ecology." His claim that ontogeny recapitulates phylogeny is now regarded as an exaggeration.

After reading Pasteur's research on germs, Lister disinfected wounds and surgical instruments with carbolic acid and dramatically lowered deaths from infection after surgery. Twenty years on, Semmelweis was proved right.

Darwin argued that humans are a product of evolution like any other organism, and put forward the theory of sexual selection to explain traits such as the peacock's tail that help in mating rather than survival.

Koch showed that the anthrax bacterium causes anthrax, and in 1882 he discovered the tuberculosis bacterium. He set out criteria for proving that a specific microbe causes a specific disease (Koch's postulates), and the technique of growing pure bacterial cultures on agar came from his lab. The pathogens behind cholera, diphtheria, plague and more were then discovered one after another.

• Robert Koch ↗
• Germ theory of disease ↗

Pasteur developed the method of inducing immunity with weakened pathogens and saved a boy bitten by a rabid dog by vaccinating him. Jenner's chance discovery had become a systematic science.

Weismann argued that hereditary information passes to offspring only through the germ cells, and that changes acquired by body cells are not passed on, rejecting Lamarck's inheritance of acquired characteristics.

Beijerinck found that the cause of tobacco mosaic disease was small enough to pass through filters that stopped bacteria, and called it a "contagious living fluid": a virus. Ivanovsky had reported the same phenomenon earlier.

• Virus ↗

Only after de Vries, Correns and Tschermak each arrived at the same laws of heredity was Mendel's paper rediscovered. In 1905 Bateson coined the word "genetics," and in 1909 Johannsen coined "gene." In the same year, in physics, Planck proposed the quantum hypothesis.

In experiments with fruit flies, Morgan found that the white-eye trait is inherited along with sex, proving that genes lie on chromosomes. In 1913 his student Sturtevant measured the distances between genes and made the first genetic map.

• Thomas Hunt Morgan ↗

Mendelian inheritance dealt with sharply distinct traits, while evolution was thought to work through small continuous variations, so the two seemed to clash. Fisher showed that continuous traits can be explained as the sum of many Mendelian genes. Along the way he created core tools of modern statistics: analysis of variance, maximum likelihood estimation and experimental design. Haldane and Wright also built mathematical population genetics.

• Population genetics ↗

Banting and Best isolated insulin, a hormone from the pancreas that lowers blood sugar, and the next year successfully treated diabetic patients. Before this, people died within a few years of diagnosis.

• Insulin ↗

Fleming noticed by chance that bacteria died around a blue mold growing on a culture plate, and when Florey and Chain achieved mass production in the 1940s, the age of antibiotics began. The same year Griffith found that something from dead disease-causing bacteria could turn live harmless bacteria dangerous. Identifying that "something" became the next challenge.

• Penicillin ↗
• Griffith's experiment ↗

Tansley coined the concept of the "ecosystem," treating organisms and their physical environment as a single system. The same year Lorenz described "imprinting," in which newly hatched goslings follow the first moving thing they see as their mother, and with Tinbergen and von Frisch (the honeybee dance) founded ethology.

• Ecosystem ↗

In Genetics and the Origin of Species, Dobzhansky connected population genetics to real organisms, and Mayr, Simpson and Julian Huxley extended it to speciation and the fossil record, completing the "modern synthesis" in the early 1940s. The same year Krebs revealed the cycle of chemical reactions by which cells extract energy from nutrients.

• Modern synthesis (20th century) ↗

Most scientists thought hereditary information must reside in complex proteins. Avery showed that the cause of the transformation Griffith had found was DNA, which seemed simple. The same year the physicist Schrödinger reasoned in What Is Life? that hereditary information must be stored in code within molecules, and many physicists inspired by the book moved into biology.

• Avery–MacLeod–McCarty experiment ↗

Hershey and Chase labeled a virus's protein and its DNA with different radioactive tags and showed that it is DNA that enters the bacterium. Earlier, Chargaff had found that DNA always contains equal amounts of A and T, and of G and C. The same year Hodgkin and Huxley explained with a mathematical model how nerve signals travel as flows of ions.

• Hershey–Chase experiment ↗

Watson and Crick revealed that DNA is a double helix of two twisted strands in which A pairs with T and G with C. The decisive clue was Rosalind Franklin's X-ray diffraction image, "Photo 51," which Wilkins had shown them without her knowledge. Franklin died young in 1958 and did not share the 1962 Nobel Prize. The principle of replication, using one strand as a template for the other, was built into the structure itself.

• Nucleic acid double helix ↗
• Rosalind Franklin ↗

Using DNA labeled with heavy nitrogen, Meselson and Stahl confirmed that when DNA replicates, each new molecule pairs one original strand with one new strand. The same year Crick proposed the "central dogma": information flows from DNA to RNA, and from RNA to protein.

• Meselson–Stahl experiment ↗
• Central dogma of molecular biology ↗

Watching chimpanzees at Gombe in Tanzania, Jane Goodall discovered that they strip the leaves from twigs to make tools for fishing termites. The definition of humans as "the toolmaking animal" was shaken.

• Jane Goodall ↗

Nirenberg found that the RNA sequence UUU specifies the amino acid phenylalanine, and by 1966 the genetic code for all 64 codons had been deciphered. The same year Jacob and Monod revealed the operon, a control system that switches genes on and off only when needed.

• Genetic code ↗

Hamilton explained the altruism of ants and bees mathematically with kin selection: helping relatives who share your genes ultimately spreads your own genes.

• Kin selection ↗

Lynn Margulis argued that the mitochondria and chloroplasts in cells were originally free-living bacteria that came to live symbiotically inside other cells. Rejected by journal after journal at first, the idea is now accepted.

• Symbiogenesis ↗

Motoo Kimura proposed the neutral theory: most genetic changes at the molecular level spread by random drift rather than natural selection. It became the theoretical basis for molecular clocks and phylogenetic analysis.

Gould and Eldredge proposed punctuated equilibrium: as the fossil record suggests, evolution alternates between long periods of stasis and brief periods of rapid change.

Cohen and Boyer developed techniques for cutting DNA with restriction enzymes, splicing it into the DNA of another organism and copying it in bacteria. Worried about the risks, scientists drew up their own research guidelines at the 1975 Asilomar Conference. In 1978 the technique got bacteria to produce human insulin.

• Recombinant DNA ↗
• Asilomar Conference on Recombinant DNA ↗

Building on the theories of Hamilton and others, Dawkins popularized the view of organisms as "survival machines" built by genes to copy themselves. The word "meme," for a unit of cultural replication, also comes from this book.

• The Selfish Gene ↗

Sanger developed a method for reading the sequence of DNA (he won the Nobel Prize twice). The same year, comparing RNA sequences, Woese discovered archaea, a group of organisms completely distinct from bacteria, and in 1990 he divided all life into three domains: bacteria, archaea and eukaryotes. Lineages began to be drawn from genes rather than outward appearance.

• Sanger sequencing ↗
• Three-domain system ↗

Louise Brown was born in Britain through the in vitro fertilization technique of Edwards and Steptoe. Millions of people have since been born this way.

• In vitro fertilisation ↗

Kary Mullis devised the polymerase chain reaction (PCR), which copies a specific stretch of DNA billions of times. He said the idea came to him while driving. The same year Barré-Sinoussi and Montagnier discovered HIV, the cause of AIDS.

• Polymerase chain reaction ↗
• HIV ↗

An international project began to read the entire sequence of the roughly 3 billion base pairs of human DNA. It was biology's first big-science project.

• Human Genome Project ↗

Wilmut and Campbell placed the nucleus of a mammary cell from an adult sheep into an egg and produced Dolly, a cloned sheep. It proved that an adult cell still holds all the information needed to build a whole animal, and it ignited an ethical debate over human cloning.

• Dolly (sheep) ↗

After a draft in 2001, the Human Genome Project was completed in 2003. One of the surprises was that humans have only about 20,000 genes, far fewer than the 100,000 expected. Next-generation sequencing later drove the cost of reading a genome down to around $1,000.

Shinya Yamanaka added four genes to adult skin cells and succeeded in returning them to a state like embryonic stem cells, able to become any kind of cell. A path to regenerative medicine without embryos opened up.

• Induced pluripotent stem cell ↗

Svante Pääbo extracted DNA from fossil bones, sequenced the Neanderthal genome and showed that modern humans interbred with Neanderthals (Nobel Prize, 2022). The same year the Venter Institute created a working bacterium run by a genome designed on a computer and synthesized chemically.

• Neanderthal genome project ↗

Doudna and Charpentier turned CRISPR, which bacteria use to fend off viruses, into a tool for cutting DNA precisely at any chosen spot (Nobel Prize in Chemistry, 2020). In 2023 the first CRISPR-based treatment, for sickle cell disease, was approved.

• CRISPR gene editing ↗

The mRNA technology that Karikó and Weissman had pursued through decades of neglect became practical within a year as COVID-19 vaccines (Nobel Prize in Physiology or Medicine, 2023). The same year AlphaFold 2 predicted the 3D structures of proteins from their amino acid sequences alone, effectively solving a 50-year-old problem.

• mRNA vaccine ↗
• AlphaFold ↗

Even the "complete" genome of 2003 had gaps, about 8% left unread because of repetitive sequences. Using new technology that reads long sequences, the T2T Consortium at last published a human genome with no gaps from end to end.

• Human genome ↗

The FlyWire consortium published a connectome mapping all of the roughly 140,000 neurons in a fruit fly's brain and the more than 50 million connections among them. It was the first complete wiring diagram of a complex brain.

• Connectome ↗