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BCc.2500 The characteristic symptoms of malaria are

first described in Chinese medical writings.

c.1000 Hindu physicians exhibit broad clinical

knowledge of tuberculosis. In India, the

Laws of Manu consider it to be an unclean,

incurable disease and an impediment to

marriage.

c.430 Plague of Athens caused by unknowninfectious agent. One third of the popula-tion (increased by those fleeing the Spartanarmy) die.

c.400 Hippocrates (460–370 BC), Greek physi-

cian, and his disciples found their medical

practice based on reason and experiment.

They attribute disease to natural causes and

use diet and medication to restore the

body’s balance of humors.

c.400 Hippocratic texts recommend irrigationwith fresh water as a treatment for septicwounds.

c.300 A medical school is set up in Alexandria

where the first accurate anatomical observa-

tions using dissection are made. The principal

exponents of the school are Greek physician

Herophilus (c.335–c.280 BC) and Greek

physician Erasistratus (c.304–c.250 BC).

c.300 Herophilus, Greek anatomist, establishes

himself as the first systemic anatomist and

the first to perform human dissections.

91 Greek scientific medicine takes hold in Romewhen the physician Asclepiades (c.130–40BC) of Bithynia settles in the West.

ADc.30 Aulus Cornelius Celsus, Roman encyclo-

pedist, writes his influential book De Re

Medicina. This work On Medicine contains

descriptions of many conditions and oper-

ations, and is probably drawn mostly from

the collection of writings of the school of

Hippocrates. It is rediscovered during the

fifteenth century and becomes highly influ-

ential. (See 1426)

c.75 Dioscorides, Greek physician, writes the first

systematic pharmocopoeia. His De Materia

Medica in five volumes provides accurate

botanical and pharmacological information.

It is preserved by the Arabs and, when trans-

lated into Latin and printed in 1478,

becomes a standard botanical reference.

150 Cladius Galen says that pus formation is

required for wound healing. This proves

to be incorrect and hinders the treatment

of wounds for centuries.

c.160 Bubonic plague (termed ‘‘barbarian boils’’)sweeps China.

c.160 Galen (c.130-c.200), Greek physician, in

his De Usu Partium describes the pineal

gland as a secretory organ that is important

to thinking. He names it the pineal because

it resembles a pine cone.

c.166 Plague in Rome (possibly smallpox or

bubonic plague) eventually kills millions

throughout the weakening Roman empire.

167 Stabiae, a popular health resort for tuber-culosis sufferers, is established near Naples,

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Italy. It is believed that the fumes fromnearby Mt. Vesuvius are beneficial for lungulcers.

170 Galen, the Greek physician, first describesgonorrhea.

c.200 Galen describes internal inflammations ascaused by personal factors.

c.370 Basil of Caesarea (330–379) founds andorganizes a large hospital at Caesarea (nearPalestine).

c.400 Fabiola, a Christian noblewoman, foundsthe first nosocomium or hospital in West-ern Europe. After establishing the first hos-pital in Rome, she founds a hospice forpilgrims in Porto, Italy.

430 Earliest recorded plague in Europe is anepidemic that breaks out in Athens, Greece.

c.500 During this century, the ‘‘plague of Justi-nian’’ kills about one million people.

529 Benedict of Nursia founds the monasteryat Monte Cassino in central Italy. Itbecomes, if not an actual medical school,at least an important center of scholarshipin which medicine played a great part. Italso acquires great fame throughout theWest and its medical teachings are spreadby the Benedictines to their monasteriesscattered all over Europe.

610 In China, Ch’ao Yuan-fang writes a treatiseon the causes and symptoms of diseases.Medical knowledge spreads from China toJapan via the Korean peninsula.

644 Rotharus, King of Lombardy also calledRothari, issues his edict ordering the seg-regation of all lepers.

c.700 Benedictus Crispus, archbishop of Milanfrom 681 to about 730, writes his Com-mentarium Medicinale, an elementarypractical manual in verse. It describes theuse of medicinal plants for curing illnesses.

c.850 Christian physician Sabur ibn Sahl of Jun-dishapur compiles a twenty-two volumework on antidotes that dominates Islamicpharmacopeia for the next 400 years.

c.850 Islamic philosopher al-Kindi (813–873)writes his De Medicinarum CompositarumGradibus, which attempts to base dosages ofmedicine on mathematical measurements.

c.875 Bertharius, the abbot of Montcasino from857 to 884, writes two treatises, De Innu-

meris Remediorum Utilitatibus and DeInnumeris Morbis that give insight intothe kind of medicine practiced in themonasteries.

896 Abu Bakr al-Razi (also known as Rhazes

(c.845-c.930), Persian physician and alchem-

ist, distinguishes between the specific charac-

teristics of measles and smallpox. He is also

believed to be the first to classify all substan-

ces into the great classification of animal,

vegetable, and mineral. (See 918)

c.900 First medical books written in Anglo-

Saxon appear. Lacnunga and the Leech Book

of Bald appear and have some botanical

sections.

c.955 Jewish ‘‘prince of medicine,’’ Isaac Israeli,

dies. He writes classic works on fever and

uroscopy, as well as a Guide of the Physicians.c.980 Abu Al–Qasim Al–Zahravi (Abucasis) cre-

ates a system and method of human dis-section along with the first formal specificsurgical techniques.

c.1000 Ibn Sina, or Avicenna, publishes Al-

Quanun, or Canon of Medicine, where he

held that medicines could be discovered

and tried by experiment or by reasoning.

1137 St. Bartholomew’s hospital is founded inLondon.

1140 Bologna, Italy, begins to develop as a

major European medical center. In the

next century, the Italian physician Taddeo

Alderotti (c.1233–1303) opens a school of

medicine there.

1200 Physicians in Italy begin to write case-

histories that describe symptoms and observ-

able pathology of diseases.

c.1267 Roger Bacon (1214–1292), English phi-

losopher and scientist, asserts that natural

phenomena should be studied empirically.

1302 First formally recorded post-mortem or

judicial autopsy is performed in Bologna,

Italy, by Italian physician Bartolomeo da

Varignana. A postmortem is ordered by

the court in a case of suspected poisoning.

1333 Public botanical garden is established in

Venice, Italy, to grow herbs that have med-

ical uses.

1345 First apothecary shop or drug store opensin London, England.

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1348 The beginning of a three-year epidemic

caused by Yersinia pestis kills almost one-

third of the population of urban Europe.

In the aftermath of the epidemic, measures

are introduced by the Italian government

to improve public sanitation, marking the

origin of public health.

1374 As the plague spreads, the Republic of

Ragusa places the first quarantines on

crews of ships thought to be infected.

1388 Richard II (1367–1400), king of England,

establishes the first sanitary laws in England.

1489 Typhus is first brought to Europe by sol-

diers who had been fighting in Cyprus.

1491 First anatomical book to contain printed

illustrations is German physician Johannes

de Ketham’s Fasciculus Medicinae.1492 Venereal diseases, smallpox, and influenza

are brought by the Columbus expedition

(and subsequent European explorers) to

the New World. Millions of native peoples

eventually die from these diseases because

of a lack of prior exposure to stimulate

immunity. In some regions, whole villages

succumb, and across broader regions up to

95% of the native population dies.

1525 Gonzalo Hernandez de Oviedo y Valdes

(1478–1557) of Spain publishes the first

systematic description of the medicinal

plants of Central America.

1525 Paracelsus (1493–1541), Swiss physician

and alchemist, begins the use of mineral

substances as medicines.

1527 Paracelsus (1493–1541), Swiss physician

and alchemist, publicly burns the writings

of Galen at Basel. He rejects the traditional

medical methods as irrational, and he

founds iatrochemistry, asserting that the

body is linked in some way to the laws of

chemistry.

1528 The Italian physician Fracastorius describes

an epidemic of typhus among French

troops invading Naples.

1530 Girolamo Fracastoro (1478–1553), Italian

physician and poet, writes his poem called

‘‘Syphilis’’ (Syphilis sive Morbus Gallici),which gives the definitive name to the sex-

ually transmitted disease that is spreading

throughout Europe.

1536 Paracelsus (1493–1541), Swiss physicianand alchemist, publishes his surgical trea-tise, Chirurgia Magna.

1543 Andreas Vesalius (1514–1564), Dutchanatomist, publishes his De CorporisHumani Corporis Fabrica, the first accu-rate book on human anatomy. Its illustra-tions are of the highest level of bothrealism and art, and the result revolutio-nizes biology.

1546 Girolamo Fracastoro (1478–1553), Italianphysician, writes his De Contagione et Con-tagiosis Morbis, which contains new ideason the transmission of contagious diseasesand is considered as the scientific begin-ning of that study.

1563 Epidemic cholera is described by Garcia delHuerto, working in Goa, India.

1567 A book on miner’s tuberculosis by Swissphysician and alchemist Paracelsus (1493–1541) is posthumously published.

1602 Felix Platter (1536–1614), Swiss anato-mist, publishes his Praxis Medica, which isthe first modern attempt at the classifica-tion of diseases.

1621 Johannes Baptista van Helmont (1577–1635), Dutch physician and alchemist,writes his Ortus Medicinae in which hebecomes one of the founders of modernpathology. He studies the anatomicalchanges that occur in disease.

1624 Adriaan van den Spigelius (1578–1625),Dutch anatomist, publishes the first accountof malaria.

1640 Juan del Vigo introduces cinchona intoSpain. Native to the Andes, the bark of thistree is processed to obtain quinine, used inthe treatment of malaria.

1642 First treatise on the use of cinchona bark(quinine powder) for treating malaria iswritten by Spanish physician Pedro Barba(1608–1671).

1648 Rene Descartes (1596–1650), French phi-

losopher and mathematician, writes DeHomine, the first European textbook on

physiology. He considers the body to be a

material machine and offers his mechanist

theory of life.

1648 Willem Piso (1611–1678), Dutch physi-cian and botanist (also called Le Pois),

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points out the effectiveness of ipecacagainst dysentery in his book De MedicinaBrasiliensi. He is among the first tobecome acquainted with tropical diseases,and he distinguishes between yaws andsyphilis.

1660 The Royal Society of London is founded inEngland with Henry Oldenburg (c.1618–1677) Secretary and Robert Hooke(1635–1702) Curator of Experiments.Two years later (1662), King Charles II(1630–1685) grants it a royal charter, andit becomes known as the ‘‘Royal Society ofLondon for the Promotion of NaturalKnowledge.’’

1665 Bubonic plague epidemic in London kills75,000 people. It is during this scourgethat English scientist and mathematicianIsaac Newton (1642–1727) leaves schoolin London and stays at his mother’ farm inthe country. There he formulates his lawsof motion.

1665 First drawing of the cell is made by RobertHooke (1635–1703), English physicist.While observing a sliver of cork under amicroscope, Hooke notices it is composedof a pattern of tiny rectangular holes hecalls ‘‘cells’’ because each looks like asmall, empty room. Although he does notobserve living cells, the name is retained.

1665 Robert Hooke (1635–1703), English phys-icist, publishes his landmark book onmicroscopy called Micrographia. Contain-ing some of the most beautiful drawings ofmicroscopic observations ever made, hisbook led to many discoveries in relatedfields.

1666 Robert Boyle (1627–1691), English phys-

icist and chemist, publishes The Origine ofFormes and Qualities in which he begins to

explain all chemical reactions and physical

properties through the existence of small,

indivisible particles or atoms.

1668 Francesco Redi (1626–1697), Italian physi-

cian, conducts experiments to disprove

spontaneous generation and shows that

maggots are not born spontaneously, but

come from eggs laid by flies. He publishes

his Esperienze Intorno all Generazione degliInsetti.

1671 Michael Ettmuller (1644–1683), Germanphysician, attributes the contagiousness oftuberculosis to sputum.

1672 French physician Le Gras introduces ipecac

into Europe as he brings it to Paris this

year. The root of the Brazilian plant ipeca-

cuanha is used to cure dysentery. (See

1625)

1674 Antoni van Leeuwenhoek (1632–1723),

Dutch biologist and microscopist, observes

‘‘animacules’’ in lake water viewed through

a ground glass lens. This observation of

what will eventually be known as bacteria

represents the start of the formal study of

microbiology.

1675 John Josselyn, English botanist, publishes

an account of the plants and animals he

encounters while living in America and

indicates that tuberculosis existed among

the Native Americans before the coming

of the Europeans.

1677 Antoni van Leeuwenhoek (1632–1723),

Dutch biologist and microscopist, discov-

ers spermatozoa and describes them in a

letter he publishes in Philosophical Trans-actions in 1679. In the same year, Johan

Ham also sees them microscopically, but

the semen he observes comes from a patient

suffering from gonorrhea, and Ham con-

cludes that spermatozoa are a consequence

of the disease.

1700 Bernardino Ramazzini (1633–1714), Ital-

ian physician, publishes the first systematic

treatment on occupational diseases. His

book, De Morbis Artificum, opens up an enti-

rely new department of modern medicine—

diseases of trade or occupation and industrial

hygiene.

1721 The word ‘‘antiseptic’’ first appears in print.

1730 George Martine performs the first trache-

ostomy on a patient with diphtheria.

1735 Botulism first described.

1748 John Fothergill describes diphtheria in‘‘Account of the Putrid Sore Throat.’’

1762 Marcus Anton von Plenciz, Sr. (1705–

1786), Austrian physician, expresses the idea

that all infectious diseases are caused by liv-

ing organisms and that there is a specific

organism for each disease.

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1767 William Heberden demonstrates that chicken-pox is not a mild form of smallpox, but adifferent disease.

1780 George Adams (1750–1795), Englishengineer, devises the first microtome. Thismechanical instrument cuts thin slices forexamination under a microscope, thusreplacing the imprecise procedure of cut-ting by hand-held razor.

1789 Polio is first described by Michael Under-wood in England.

1796 Edward Jenner (1749–1823) uses cowpoxvirus to develop a smallpox vaccine. Bymodern standards, this was human experi-mentation as Jenner injected healthy eight-year-old James Phillips with cowpox andthen after a period of months with smallpox.

1798 Government legislation is passed to estab-lish hospitals in the United States devotedto the care of ill mariners. This initiativeleads to the establishment of a HygenicLaboratory that eventually grows tobecome the National Institutes of Health.

1800 Marie-Francois-Xavier Bichat publishes hisfirst major work, Treatise on Tissues, whichestablishes histology as a new scientific disci-pline. Bichat distinguishes 21 kinds of tissueand relates particular diseases to particulartissues.

1801 A hospital is established in London, Eng-land, to treat the victims of typhus.

1802 John Dalton introduces modern atomictheory into the science of chemistry.

1814 The Royal Hospital for Diseases of theChest is founded in London, England, inan attempt to keep consumptive patients(people with tuberculosis) segregated.

1816 The stethoscope, which is an importanttool for diagnosing pneumonia, is intro-duced by Rene LaEnnec.

1817 Start of first cholera pandemic, whichspreads from Bengal to China in the eastand to Eygpt in the west.

1818 William Charles Wells suggests the theoryof natural selection in an essay dealingwith human color variations. He notes thatdark-skinned people seem more resistant totropical diseases than lighter-skinned peo-ple. Wells also calls attention to selectioncarried out by animal breeders. JeromeLawrence, James Cowles Prichard, and

others make similar suggestions, but donot develop their ideas into a coherentand convincing theory of evolution.

1818 Xavier Bichat (1771–1802), French physi-

cian, publishes his first major work, Trait,

des membranes en general, in which he pro-

pounds the notion of tissues. This work also

founds histology, distinguishing 21 kinds of

tissue and relating disease to them.

1820 First United States Pharmacopoeia is

published.

1824 Start of second cholera pandemic, which

penetrates as far as Russia and also reaches

England, North America, the Caribbean,

and Latin America.

1826 Pierre Bretonneau (1778–1862), French

physician, describes and names diptheria

in his specification of diseases.

1829 Salicin, the precursor of aspirin, is purified

from the bark of the willow tree.

1831 Charles Robert Darwin (1809–1882) beginshis historic voyage on the H.M.S. Beagle(1831–1836). His observations during thevoyage lead to his theory of evolution bymeans of natural selection.

1835 Jacob Bigelow (1787–1879), American

physician, publishes his book On Self-

Limited Diseases in which he states the com-

monsense idea that some diseases will sim-

ply run their course and subside without the

benefit of any treatment from a physician.

1836 Theodor Schwann carries out experiments

that refute the theory of the spontaneous

generation. He also demonstrates that alco-

holic fermentation depends on the action

of living yeast cells. The same conclusion is

reached independently by Charles Caignard

de la Tour.

1837 Pierre-Francs-Olive Rayer (1793–1867),

French physician, is the first to describe

the disease glanders as found in man and

to prove that it is not a form of tuberculosis.

1838 Angelo Dubini (1813–1902), Italian physi-

cian, discovers Ankylostoma duodenale, the

cause of hookworm disease, in the intestinal

tract.

1838 Matthias Jakob Schleiden notes that the

nucleus first described by Robert Brown is

a characteristic of all plant cells. Schleiden

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describes plants as a community of cells

and cell products. He helps establish cell

theory and stimulates Theodor Schwann’s

recognition that animals are also composed

of cells and cell products.1839 Third cholera pandemic begins with entry

of British troops in Afghanistan and travelsto Persia, Central Asia, Europe, and theAmericas.

1841 Friedrich Gustav Jacob Henle (1809–1885), German pathologist and anatomist,publishes his Allegemeine Anatomie, whichbecomes the first systematic textbook ofhistology (the study of minute tissue struc-ture and includes the first statement of thegerm theory of communicable disease).

1842 Edwin Chadwick, a pioneer in sanitaryreform, reports that deaths from typhus in1838 and 1839 in England exceeded thosefrom smallpox.

1842 Oliver Wendell Holmes recommends thatsurgeons wash their hands using calciumchloride to prevent spread of infectionfrom corpses to patients.

1843 First outbreak of polio in the United Statesoccurs.

1843 Gabriel Andral (1797–1876), French physi-cian, is the first to urge that blood be exam-ined in cases of disease.

1846 American Medical Association establishes acode of ethics for physicians which declarestheir obligation to treat victims of epidemicdiseases even at a risk to their own lives.(See 1912)

1847 A series of yellow fever epidemics sweepsthe American Southern states. The epi-demics recur for more than thirty years.

1847 The first sexually transmitted disease clinicis opened at the London Docks Hospital.

1849 John Snow (1813–1858), English physi-

cian, first states the theory that cholera is

a water-borne disease. During a cholera

epidemic in London in 1854, Snow breaks

the handle of the Broad Street Pump,

thereby shutting down the main source of

disease transmission during the outbreak.1849 John Snow publishes the groundbreaking

paper ‘‘On the Transmission of Cholera.’’1855 Third, or Modern, pandemic of plague

probably begins in Yunan province, China.

1857 Louis Pasteur demonstrates that lactic acidfermentation is caused by a living organ-ism. Between 1857 and 1880, he performsa series of experiments that refute thedoctrine of spontaneous generation. Healso introduces vaccines for fowl cholera,anthrax, and rabies, based on attenuatedstrains of viruses and bacteria.

1858 Rudolf Ludwig Carl Virchow publishes hislandmark paper ‘‘Cellular Pathology’’ andestablishes the field of cellular pathology.Virchow asserts that all cells arise from pre-existing cells (Omnis cellula e cellula). Heargues that the cell is the ultimate locus ofall disease.

1859 Charles Robert Darwin publishes his land-mark book On the Origin of Species by Meansof Natural Selection.

1861 Carl Gegenbaur confirms Theodor Schwann’ssuggestion that all vertebrate eggs are sin-gle cells.

1862 First demonstration of pasteurization.

1864 Fourth cholera pandemic starts and revisitslocations of previous pandemics.

1865 An epidemic of rinderpest kills 500,000cattle in Great Britain. Government inqui-ries into the outbreak pave the way for thedevelopment of contemporary theories ofepidemiology and the germ theory ofdisease.

1865 French physiologist Claude Bernard pub-

lishes Introduction to the Study of HumanExperimentation, which advocates ‘‘Never

perform an experiment which might be

harmful to the patient even if advantageous

to science. . ..’’

1866 The Austrian botanist and monk JohannGregor Mendel (1822–1884) discovers thelaws of heredity and writes the first of aseries of papers on heredity (1866–1869).The papers formulate the laws of hybridiza-tion. Mendel’s work is disregarded until1900, when Hugo de Vries rediscovers it.Unbeknownst to both Darwin and Mendel,Mendelian laws provide the scientific frame-work for the concepts of gradual evolutionand continuous variation.

1867 Joseph Lister publishes a study that impli-cates microorganisms with infection. Basedon this, his use of early disinfectants during

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