A Selected Chronological Bibliography of Biology and Medicine


 Part 1B





Compiled by James Southworth Steen, Ph.D.

Delta State University


Dedicated to my loving family


This document celebrates those secondary authors and laboratory technicians without whom most of this great labor of discovery would have proved impossible.


Please forward any editorial comments to: James S. Steen, Ph.D., Professor Emeritus, DSU Box 3262, Cleveland, MS 38733. jsteen08@bellsouth.net



René Descartes (FR) within his Discourse on Method, Optics, Geometry, and Meteorology explained his principles of investigation: "The first of these was to accept nothing as true which I did not clearly recognize to be so: that is to say, carefully to avoid precipitation and prejudice in judgments and to accept in them nothing more than what was presented to my mind so clearly and distinctly that I could have no occasion to doubt it. The second was to divide up each of the difficulties which I examined into as many parts as possible, and as seemed requisite in order that it might be resolved in the best manner possible. The third was to carry on my reflections into order, commencing with objects that were the more simple and easy to understand, in order to rise little by little, or by degrees, to knowledge of the most complex assuming order, even it be a fictitious one, among those which do not follow a natural sequence relatively to one another. The last was in all cases to make enumerations so complete and reviews so general that I should be certain of having omitted nothing."

Included within one of the Essays is La Dioptrique, the first publication of the “Law of Refraction”, in which he demonstrates the rectilinear transmission of light and compares the human eye to a camera. Rene Descartes (444; 446; 448).


Thomas Morton (GB) wrote New English Canaan (1637) with treatments of 26 species of mammals, 32 birds, 20 fishes and 8 marine invertebrates (1074).



Galileo Galilei (IT) worked out the isochronism of the pendulum in the Cathedral of Pisa using his pulse (577; 578).


The Countess of Chinchon (ES), wife of the Viceroy of Peru, was cured of a fever (malaria; the ague) by powdered quinquina (cinchona) bark, a native remedy. She returned to Spain in 1641 with a supply of quinquina bark, which became known in Europe as the Countess’s powder. Later it was imported in large quantities by the Jesuits and became known as Jesuit’s bark. The tree was described in 1738 and given the genus name Chinchona in honor of the Countess.

Juan del Vego (ES), physician to the countess, in 1641, was the first European to employ the tincture of the cinchona bark, containing quinidine, for treating malaria (the ague). The aborigines of Peru and Ecuador had been using it for treating fevers since before recorded time (119; 918).

Hermann van der Heyden (BE) authored Discours et Advis sur les Flus de Ventre Doloureux. It contains the first European medical reference to cinchona bark (Peruvian bark) for treating malaria (the ague) (1593). This remedy was also known as quina bark (contains quinine) and later as the Countesse’s powder and Jesuit’s bark.

Nicolas de Blégny (FR) and John Talbor (GB) popularized a treatment for malaria, the ague in England and France. Tabor became wealthy and famous yet refused to divulge his formula for financial and religious/political reasons. At that time anything associated with the Catholic Church was out of favor in England. Talbor’s treatment was nothing more than the hated Jesuit’s Powder (ground cinchona bark containing quinine) which the catholic church had been shipping from South America and Cardinal John de Lugo had tried in vain to persuade Europe to accept (385; 1539).

Richard Morton (GB), in 1696, presented the first detailed description of the clinical picture of malaria (the ague) and its treatment with cinchona (1073).

Francisci Torti (IT), in 1732, established the specific nature of cinchona bark (contains quinine). His demonstration of its effectiveness in treating periodic over continuous fevers finally overthrew the doctrine of the common origin of all fevers. He is also credited with the introduction of the term malaria (bad air) (1559).

Hipólito Ruiz (ES), in 1792, described seven species of cinchona and praised the medicinal qualities of a quina extract that he had developed (contains quinine) (1318).

Bernardino Antonio Gomes (PT) reported that the bark of grey quinquina (Cinchona condaminea) from Loxa (Loja, Ecuador) contained a crystalline principle that he named cinchonine but did not notice its main property, alkalinity (616).

Pierre-Joseph Pelletier (FR) and Joseph-Bienaimé Caventou (FR) isolated the alkaloid quinine (1166; 1167).

Peter Muehlens (DE) synthesized plasmochin (plasmoquine), the first drug to be synthesized with a marked activity against human malaria parasites (1076).

Ernest Francois Auguste Fourneau (FR), Jacques Gustave Marie Tréfouel (FR), G. Stefanopuolo (FR), Yvonne de Lestrange (FR), K.L. Melville (FR), Thérèse Tréfouel (FR), Daniel Bovet (FR), Melle Germaine Benoit (FR), Onisim Yul'yevich Magidson (RU),  and I.Th. Strukow (RU) produced plasmocid (Fourneau 710) and 8-aminoquinoline, active antimalarial drugs (560; 561; 968).

Hans Mauss (DE) and Fritz Mietzch (DE), in 1931, synthesized the antimalarial drug mepacrine hydrochloride (quinacrine hydrochloride, Atabrine quinacrine, mepacrine, atebrin, chinacrin, erion, acriquine, acrichine, palacrin, metoquin, halchin) (1005). It was marketed in 1932.

Hans Andersag (DE), in 1934, synthesized resochin (chloroquine) (37).

Frank Henry Swinton Curd (GB), D. Garnet Davey (GB), and Francis Leslie Rose (GB) synthesized proguanil (paludrine) in 1944. This drug has low toxicity and high activity against falciparum malaria. They first tested proguanil against avian malaria in 1945 (341; 1309).

M.B. Braude (RU) and V.I. Stavrovskaya (RU) synthesized quinocide in 1945 (201).

Neil Hamilton Fairley (AU) proved that one tablet of Atabrine (100 mg.) a day would prevent overt attacks of malaria (the ague), curing those cases due to Plasmodium falciparum and postponing clinical manifestations of P. vivax infections until the drug was withheld (511).



Guillaume de Baillou; William of Ballion; Wilhelm Ballonius (FR) wrote, Epidemiorum et Ephemeridum Libri Duo, the first modern book on epidemiology and the first since Hippocrates. It contains the first detailed description of whooping cough as a distinct entity (384).



Nicolaas Tulp; Nicholas Tulpius; Nicolaes Tulp; Claes Pieters; Nicolaus Petrejus; Nicholaus Petrus (NL) wrote, Observationes Medicae, one of the best medical books of the period. It contained many pathological findings and records of post-mortem examinations. It described and pictured the ileocecal valve, still known as Tulp’s valve, and discussed kidney stones, tapeworms, diphtheria, bronchial casts, pulsation of the spleen, and beri-beri (1570). Tulp described the first of the great apes (a chimpanzee) brought alive to Europe in 1641. Rembrandt van Rijn (NL) immortalized him in his painting The Anatomy Lesson of Dr. Tulp.

Francois de Le Boë; Franciscus Sylvius (DE-NL) described a fissure on the lateral surface of the brain (901). Caspar Bartholin (DK) commemorated him by naming it the Sylvian fissure (80).


Moritz Hoffmann (DE), in 1641, claimed to have described the ductus pancreaticus (duct of Wirsüng, Hoffmann’s duct), the main excretory duct of the pancreas in the turkey. This work was not published.

Johann Georg Wirsüng (DE) discovered the pancreatic duct in man yet incorrectly thought it was a chyliferous vessel originating in the intestine and entering the pancreas (1786).



Charles Bouvard (FR), the king's physician, had probably prescribed 47 bloodlettings during the last 10 years of Louis XIII of France who died of Crohn’s disease at the age of 42 years (276).



René Descartes (FR) proposed the idea for the Nebular Hypothesis. It stated that the solar system formed because "God sent adrift a number of 'vortices' of swirling gas, and these eventually made the stars, which later changed themselves into comets, which in turn still later formed themselves into planets" (447).


Evangelista Torricelli (IT) sent a letter to Michelangelo Ricci in Rome describing his invention, the barometer (1558).


Jean Claude de la Courvée (FR), in 1644, performed the first symphysiotomy (division of the fibrocartilage of the symphysis pubis, to facilitate delivery). The operation was performed to save the life of the child after the death of the mother.

Jean-Réne Sigault; Joseph Aignan Sigaud de Lafond (FR) and Alphonse Louis Vincent Leroy (FR) performed the first division of the symphysis pubis to enlarge the pelvic outlet and thus facilitate childbirth by a women deformed by rachitis; the mother and child survived (1435; 1436).


James Vaughan (GB) wrote a paper on symphysiotomy (1652).



Marco Aurelio Severino (IT) published his Zootomia Democritaea, the culmination of forty years of anatomical research, in which he discusses his research on the similarities that unify the living beings. It is widely considered the first work of comparative anatomy (1428).



Athanasius Kircher (DE-IT), following his early work with the microscope, speculated that disease and decay might be brought about by the activities of tiny living creatures. He says that with the aid of two convex lenses, held together in a tube, he observed ‘minute ”worms” in all decaying substances’ —in milk, in the blood of persons stricken with fever, and in the spittle ‘of an old man who had lived soberly’ (845; 846). He observed microorganisms in the blood of patients (847).


Wilhelm Fabry; Wilhelm Fabricius Hildanus (DE) was the first well-educated barber-surgeon in Germany. He pioneered amputation above the diseased part in gangrene, invented many surgical instruments, was the first to recognize congenital pyloric stenosis, and the first Western European to use the magnet for removal of iron splinters in the eye (509).



Yellow fever is epidemic in the West Indies.



Yellow fever killed more than 5,000 people in Barbados, and spread from there to Mexico, Cuba, and elsewhere. A second outbreak in 1691 killed many of the British settlers in Barbados, who had arrived since the earlier outbreak, whereas older natives were by this time immune (858).



Jan Baptiste van Helmont; Joannes Baptiste van Helmont; Joan Baptiste van Helmont; Johannes Baptiste van Helmont (NL) determined that the gas given off by burning charcoal is the same as that given off by fermenting grape juice. He called it spiritus silvestre (“wild spirit”). Today we recognize this as the discovery of carbon dioxide. He speculated that the process of digestion supplies heat to the body (1596).

Joseph Black (GB) rediscovered carbon dioxide, which he called fixed air, by showing that it is released when magnesium carbonate or calcium carbonate are heated. He identified the carbon dioxide thus prepared with that formed in combustion and fermentation by showing that when the gas was passed into limewater the carbonate of lime was generated. He was the first to breath into limewater and observe the formation of a precipitate of calcium carbonate. This experiment was to influence Antoine Laurent Lavoisier’s (FR) conclusion that respiration involves combustion within the body. Black is also credited with discovery of the specific heats of substances (145-148).


Georgius Marcgravus (DE), Willem Piso (NL), Johannes de Laet (BE-NL), and Franciscus Hackius (NL) described among other animals 100 species of fish indigenous to the Brazilian coastline (1195).


Another smallpox (red plague) outbreak spread to many towns in the Massachusetts colony. By this time there had been many children born in the colony who were susceptible. A simultaneous epidemic of whooping cough added to the severity of the epidemic, and to the overall death toll (858).


In response to epidemics of yellow fever in Barbados, Cuba, and the Yucatan, a strict quarantine was established in Boston, Massachusetts, for all ships arriving from the West Indies because of “ye plague or like in[fectious] disease.” (1029)



René Descartes (FR), in 1649, postulated that impulses originating in the sensory receptors of the body were carried to the central nervous system where they activated muscles by what he called reflection (445).

Jean Astruc (FR) compared the transformation of an impression or sensation into a motor discharge to a ray of light reflected on a surface; he called it a reflex (57).

Gerard Blasius; Gerhard Bläes; Gerardus Leonardus Blasius (NL) was the first to provide a demonstration of the origin of the anterior and posterior spinal nerve roots and a differentiation between the gray and white matter of the spinal cord. He was the first to illustrate clearly the H shape of gray matter in a cross-section of the spinal cord (154; 155).

Domenico Mistichelli (IT) identified the crossing of motor fibers at the ventral surface of the medulla oblongata (1048).

Francois Pourfour du Petit (FR) gave a brief account of the internal structure of the spinal cord, one of the first descriptions having significant merit, and presented his theory of contralateral innervation (1212).

Francois Pourfour du Petit (FR), in 1712, showed that the origin of the sympathetic nerves is not the cranium. He later cut the cervical sympathetic nerves in the dog and noted that this affected pupil size, the nictitating membrane, and secretions from the eye. He described the decussation of the pyramids more accurately and in greater detail than his predecessors and was among the first to deduce that the right side of the brain must control the left side of the body, whereas the left side of the brain must control the right side of the body (1213).

Johann Jakob Huber (CH) gave the first detailed and accurate descriptions of the spinal cord, spinal roots, and denticulate ligaments (778).

Robert Whytt (GB) removed known regions of the central nervous system and studied how animals reacted thereafter to various stimuli. He established that the spinal cord is essential for reflex action, described the pupillary response to light, Whytt’s reflex, noting that destruction of the anterior corpora quadrigemina abolished the reaction. He reasoned that the reception of sensory input was distributed throughout the brain and spinal cord (1766).

Felix Vicq-d'Azyr (FR) established the arrangement of the fiber bundles of the spinal cord into a posterior and two lateral columns and a white anterior commissure (1660).

Karl Friedrich Burdach (DE) described the fasciculus cuneatus (247).

Marshall Hall (GB) introduced the concept that the spinal cord is a chain of segments whose functional units are separate reflex arcs. He demonstrated tonic closure of the sphincters by reflex action, cessation of strychnine convulsions after destruction of the spinal cord, and that most reflexes are more readily elicited by stimulating appropriate end-organs than through their bared nerve trunks. He coined the use of the phrase reflex action to describe these functions (661; 1721).

Benedict Stilling (DE) and Joseph Wallach (DE) devised a microtome which enabled him to cut frozen or alcohol hardened, thin sections and examine them, unstained, with the microscope. They were the first to study the spinal cord in serial sections (1497).

Charles-Édouard Brown-Séquard (FR) found that the posterior columns of the spinal cord convey some sensory impressions. The most important sensory pathways were found to cross in the cord and, if anything, damage will cause hypersensitivity on the ipsilateral side of the spinal cord. Paralysis, loss of muscle sense, hyperasthesia to touch and painful stimuli, and conservation of sensation to cold and warmth, all appeared on the same side as spinal cord lesions. On the opposite side voluntary movement and an intact muscle sense were conserved, however there was a loss or diminution of pain, warmth, cold, and touch (225-227; 231-234).

Ludwig Türck (AT) described the ventral corticospinal tract (1571), and divided the cord into six pathways or tracts: two anterior, two lateral, and two posterior (1572).

Charles-Édouard Brown-Séquard (FR) is associated as a clinician with the description of the syndrome following spinal cord hemi-section, the so-called Brown-Séquard paralysis, characterized by the loss of motor power and position sense on the side of the lesion, with loss of pain and thermal sensibility on the side opposite the lesion. His experiments showed that the principal conduction of sensation in the cord is in the central grey matter and anterior columns, rather than in the conventionally accepted posterior columns (228-230).

Jacob Augustus Lockhart Clarke (GB) described the dorsal nucleus of the spinal cord. A column of large neurons located in the base of the posterior grey column (columna dorsalis) of the spinal cord, extending from the first thoracic through the second lumbar segment. The neurites reach out into the side-chord to form tractus spinecerebellaris posterior (295). These are called Clarke’s columns.

Friedrich Goll (CH) described the fasciculus gracilis (carries proprioception from the lower limbs and lower trunk) within the spinal cord (column or tract of Goll) (614).

Paul Emil Flechsig (DE) demonstrated the dorsal spinocerebellar tract within the spinal cord (527).

William Richard Gowers (GB) delineated the ventral spinocerebellar tract within the spinal cord (619).

Heinrich Lissauer (DE) demonstrated the tractus dorsolateralis - the poorly myelinated fibers capping the apex of the posterior horn in the spinal cord (931).

Henry Charlton Bastian (GB) provided the basis for what became Bastian's law: a transverse lesion of the spinal cord above the lumbar enlargement results in abolition of the tendon reflexes of the lower extremities (92).

Constantin von Monakow (RU-CH) described the rubrospinal tract within the spinal cord (1704).

Joseph Jules Déjérine (CH-FR) described radicular myotomes and dermatomes, the somatotopy and connections of the pyramidal tracts, as well as the lateral and ventral spinothalamic tracts. He demonstrated the lateral and anterior spinothalamic tracts (the faisceau en croissant de Dejerine) (438).

Bror Rexed (SE) divided the grey matter of the spinal cord of the cat into 10 (I-X) laminae based on groupings of neuronal size and distribution. Each contained functionally distinct neurons and axonal projections (1283). See, Herophilus, c. 300 B.C.E.; Galen, c. 175; Fernel, 1526; Ridley, 1695; Descartes, 1649.


William Harvey (GB) became convinced that systole, rather than diastole, is the active part of the cardiac cycle that begins first in the atria (681; 686).


A smallpox (red plague) epidemic passes through London.


c. 1650

The specific expression, "Above all, do no harm" and its even more distinctive associated Latin phrase, Primum est ut non nocere, has been traced back to an attribution to Thomas Sydenham (GB), c. 1650 (820; 1441).

Hippocrates (GR), in 400 B.C.E. wrote, "The physician must be able to tell the antecedents, know the present, and foretell the future- must mediate these things, and have two special objects in view with regard to disease, namely, to do good or to do no harm" (743).



Jean Bauhin (FR-CH), Johann Heinrich Cherler (CH) in their Historia Plantarum Universalis, dealt with approximately 5,000 plants. They were among the first, after Aristotle, to distinguish the species from the genus (96). Bauhin is commemorated with the genus Bauhina.


Joannus Jonstonus; Jan Jonston (PL) replaced Mollia with the term Mollusca (830).


Francis Glisson (GB) wrote the first authoritative monograph published in England dealing with a single disease, rickets (Old English, wrikken, to bend or twist) (601; 603).

Henry R. Viets (GB) had earlier written a less authoritative treatise on rickets (1761; 1762).



"Almost all animals, even those which bring forth their young alive, and man himself, are produced from eggs.” Often quoted as “omne vivum ex ovo." William Harvey (683)

Note: The mammalian ovum was discovered nearly two centuries later. See, von Baer, 1827.


"The blood is the first engendered part, whence the living principle in the first instance gleams forth, and from which the first animated particle of the embryo is formed; that it is the source and origin of all other parts, both similar and dissimilar, which thence obtain their vital heat and become subservient to it in its duties." William Harvey (682).


Nathaniel Highmore (GB) and William Harvey (GB) were among the first people to carefully study the embryonic development of chickens, concluding that all life comes from eggs. Harvey described in detail the anatomical changes occurring in the uterus of the deer during pregnancy and gave evidence that the ancient doctrine stating that the male semen functioned to organize matter contained within the uterus was incorrect (682; 683; 685; 735). Note: This work is viewed as original because it brought embryology out of the Dark Ages. Highmore's account of the development of the chick is the first embryological study based on microscopical examination predating Marcello Malpighi by more than twenty years. It was published within weeks of William Harvey's book. Harvey and Highmore had collaborated on embryological research at Oxford since the 1640's.


William Harvey (GB) described the air sacs of birds in detail (683). See, Frederick II, c. 1240.


Jean Pecquet (FR) and Johannes van Horne (DK) discovered that in dogs the cisterna chyli (receptaculum chyli) flow into the thoracic duct (ductus thoracius) which in turn opens into the veins at the union of the jugular and subclavian (1163; 1164; 1599). See, Bartolomeo Eustachi, 1552.

Olof Rudbeck the elder (SE) discovered that the lacteals of Aselli drain into the receptaculum chyli, thence into the thoracic duct and thence into the great veins of the neck, and that on opening the duct’s milky chyle flows out in profusion if, before the experiment, the animal has been well fed (1119; 1316; 1481).

Thomas Bartholin; Bartholinus (DK) and his assistant Michael Lyser (DK) reached a very similar conclusion in man: that the lymphatics formed a hitherto unrecognized physiological system which eventually collects into the thoracic duct which enters the circulation at the left subclavian vein. They were the first to find the thoracic duct in man and to realize that lymph is carried away from the liver to the thoracic duct (81; 82; 85; 86).

William Hunter (GB) rediscovered lymphatic vessels in man when he reported, "that they are the same as the lacteals, and that these together constitute one great general system dispersed through the whole body for absorption; that this system only does absorb, and not the veins; that it serves to take up and convey whatever is to make or to be mixed with the blood, from the skin, from the intestinal canal, and from all the internal cavities or surfaces whatever" (796). See, Hewson, 1771.

Alexander Monro, secundus (GB) showed that the lymphatics are absorbents and distinct from the circulatory system (1056).


Nathaniel Highmore (GB) discovered the maxillary sinus and the mediastinal testis (734).


Leopoldina was founded in the Holy Roman Empire in what is now Italy. It is the oldest continuously existing learned society in the world.



Jan Baptiste van Helmont; Joannes Baptiste van Helmont; Joan Baptiste van Helmont; Johannes Baptiste van Helmont (NL) wrote Ortis Medicinae in which he described how he performed a famous experiment. He grew a willow tree in a weighed quantity of soil and showed that after five years, during which time he only added water; the tree had gained 164 pounds while the soil had lost only two ounces. Although he incorrectly concluded that the tree converted the water into its own tissues, this is possibly the first application of a quantitative method to a biological problem.

He made gravimetric studies of urine and is credited with the discovery of carbon dioxide and emphasizing the use of the balance in chemistry and coining the word gas. He described gastric digestion in the terms of fermentation and states that there is an acid ferment in the stomach but the acid itself is not the ferment. The acid chyme of the stomach passes into the duodenum where it becomes alkaline and a second ferment is supplied by the bile. He is considered the founder of the iatro-chemical school of medicine (1597; 1598).

John Hunter (GB) later said, "These appearances throw considerable light on the principle of digestion, and show that it is neither a mechanical power, nor contractions of the stomach, nor heat, but something secreted in the coats of the stomach, and thrown into its cavity, which there animalizes the food or assimilates it to the nature of the blood. The power of this juice is confined or limited to certain substances, especially of the vegetable and animal kingdoms; and although this menstruum is capable of acting independently of the stomach, yet it is indebted to that viscus for its continuance." (784)

Edward Stevens (GB) had a human subject swallow large silver containers with perforations “capable of admitting a needle.” The containers were recovered some thirty-six to forty-eight hours later, after they had passed through the digestive tract. He tested beef, pork, cheese, pheasant, vegetables of different sorts, and cereal grains. Usually the foods were found to have been completely dissolved, but unbroken cereal grains appeared not to have been altered. Ivory balls were dissolved and disappeared (1460; 1462; 1496).

Lazzaro Spallanzani (IT) swallowed linen bags containing various foodstuffs to study the action of digestion upon the contents. He studied the action of saliva on foodstuffs and was among the first to isolate human gastric juice for study (1459; 1461).

Lazzaro Spallanzani (IT) obtained stomach juice from people with a little sponge on a thread, which people swallowed, and which was removed. The experiment showed that the stomach juice dissolves meat but does not dissolve a flower. This work discovered that the gastric juice is acidic and contains hydrochloric acid (1460).

Luigi Valentino Brugnatelli (IT) studied the gastric juice from sheep, cats, fish, and birds. He determined that it is acidic in carnivores while in herbivores it is alkaline and putrescent. He ascertained that the gastric juice of carnivorous animals had great curative powers when applied to foul ulcers or wounds, but that of herbivorous animals was destitute of this property. He succeeded in determining the solvent powers of the gastric juice from birds on metals, calcareous stones, rock crystal, and agate (236-238).

Bassiano Carminati (IT) found that gastric juice is not acidic in carnivorous animals when fasting, but quite acidic in those that had eaten. He discovered that gastric juice of carnivores could be used successfully to treat foul ulcers or wounds (267).


"an unknown affection occurred at Leipzig in 1652 and returned again in 1665. It attacked puerperal women and was so deadly that but one in ten escaped". (250; 1141; 1410) Note: very likely what was later called puerperal fever


The Academia Naturae Curiosorum was founded. It later became Kaiserlich Leopoldinisch Carolinische Deutsche Akademie der Naturforscher [Royal Leopold and Caroline German Academy of Natural Sciences].



Pierre Borel; Petri Borelli () and Isaac Cattier; Isaaci Cattieri () were the first to observe and describe a free-living nematode, which was dubbed the "vinegar eel" (178).


William Harvey (GB) was the first to describe the communication of the avian pulmonary air-passages with air sacs in the abdominal cavity (684).

John Hunter (GB), in 1758, demonstrated that the air sacs of some birds extend into their bones. He proved that birds' bones are hollow and contain air sacs by blocking the windpipes of chickens and hawks then cutting through their wings. The birds could yet fill their lungs with air, though with great difficulty, by taking in air through their severed wing bones (785; 789).



Francis Glisson (GB) described the passage of blood from the portal vein to the vena cava, and proved that lymph flows not to the liver, as was then believed, but from it, passing to the recently discovered capsula communis. He is remembered for his description of the fibrous sheath enveloping the portal vein, hepatic artery and duct, still known as Glisson’s capsule. He  believed that bile is excrement derived from the portal blood with blood purified by the liver returning to circulation by way of the vena cava (602).


Francis Glisson (GB) carried out the most detailed investigation of the liver anatomy up to this point in history (602).


Francis Glisson (GB) described the sphincteric fibers around the terminus of the common bile duct (602).

Ruggero Oddi (IT) later described these same fibers (1124). They became known as Oddi’s sphincter.



Thomas Willis (GB) wrote a book on the epidemic of “Camp Fever” (typhus) in the winter of 1655 (1779).

John Huxham (GB) distinguished between slow nervous (typhoid) and putrid malignant (typhus) fevers (813).

James Lind (GB) studied typhus then recommended delousing, viz., bathing, clean apparel, and baking of lice-ridden clothing in ovens (922).

Francesco Enrico Acerbi (IT) postulated that typhus is caused by parasites capable of entering the body and multiplying there to produce disease (10).

William Wood Gerhard (US) presented a differential diagnosis of typhus and typhoid fevers (593).

Charles Murchison (GB) stated that to prevent endemic typhus one must protect the individual from lice (1093).

Osip Moczutkowski (RU) proved that the etiological agent of endemic typhus is present in the blood during the febrile period by inoculating himself with such blood (1049).

Charles Jules Henri Nicolle (FR), Charles Compte (FR) and Ernest Conseil (FR) reported that the body louse, Pediculus vestimenti, transmits typhus fever from person to person (1115; 1117).

Howard Taylor Ricketts (US) and Russell M. Wilder (US) described a bacterium, later named Rickettsia prowazekii, found in the gut of lice feeding on typhus patients (1284; 1285).

Harry Plotz (US), Peter K. Olitsky (US), and Geoege Baehr (US) isolated and identified the etiological agent of typhus fever as Rickettsia prowazekii (1199; 1200).

Harry Plotz (US), Peter K. Olitsky (US), and George Baehr (US) developed a vaccine that proved effective against typhus fever (1201).

Henrique da Rocha-Lima (BR) showed that the bacterium which Ricketts and Wilder found in the gut of lice feeding on typhus patients, is an intracellular parasite and very likely the cause of typhus. He named the organism Rickettsia prowazekii in honor of Howard Taylor Ricketts (US), who had died in 1910 of typhus fever during an investigation of that disease, and Stanislas Josef Matthias von Prowázek (CZ) who also died of typhus while studying it (353).

Edmund Weil (AT) and Arthur Felix (PL-GB) reported that the sera of patients suffering from typhus agglutinate certain strains of the bacterium Proteus, originally isolated from the urine of a typhus fever victim. The OX-2 and OX-19 strains of Proteus are commonly used. Serum from normal persons did not produce a similar result (1738-1740). Later studies showed that Proteus spp. are not the cause of typhus fever and that antibodies against Proteus spp. normally occur quite commonly in humans. Today this procedure is called the Weil-Felix Test.

Mather H. Neill (US) discovered that scrotal reactions of guinea pigs with Mexican typhus (later known as murine typhus) could be used as a differential test with European, or epidemic, typhus. It was first known as the Neill phenomenon; later called the Neill-Mooser phenomenon after Neill and Herman Mooser, a Swiss pathologist working in Mexico (1061; 1105). 

William Fletcher (MY) and J.E. Lesslar (MY) found that the Proteus OX-K strain appears specifically to agglutinate with antibodies to Rickettsia tsutsugamushi (528).

Kenneth Fuller Maxcy (US) identified an "endemic" form of typhus fever (Brill’s disease) in the Southeastern United States and suggested that some parasite of the rat might be its vector (1006).

Rolla Eugene Dyer (US), Elmer T. Ceder (US), Adolph S. Rumreich (US), and Lucius F. Badger (US) made the first isolation of murine typhus from rat fleas. The fleas were collected at an outbreak of typhus fever in Baltimore, MD (486). Along with Elmer T. Ceder (US) and Ralph Dougall Lillie (US) they showed that the rickettsia of murine typhus persisted in rat fleas for at least nine days and were present in feces of infected fleas. They were also successful in experimental transmission of murine typhus from rat to rat with the flea Xenopsylla cheopis Rothschild (485).

M. Ruiz Castañeda (MX) and Samuel J. Zia (MX) found that there is a common antigenic factor in Rickettsia and Proteus X-19 which explains the Well-Felix reaction (271).

Hans Zinsser (US) demonstrated that Brill's disease is identical to Old World typhus caused by Rickettsia prowazeki da Rocha Lima (1202; 1814-1816). The disease was renamed Brill-Zinsser’s disease.

Herald Rea Cox (US) and E. John Bell (US) developed a formalinized rickettsial vaccine for epidemic typhus (327; 328).

Michael P. McLeod (US), Xiang Qin (US), Sandor E. Karpathy (US), Jason Gioia (US), Sarah K. Highlander (US), George E. Fox (US), Thomas Z. McNeill (US), Huaiyang Jiang (US), Donna Muzny (US), Leni S. Jacob (US), Alicia C. Hawes (US), Erica Sodergren (US), Rachel Gill (US), Jennifer Hume (US), Maggie Morgan (US), Guangwei Fan (US), Anita G. Amin (US), Richard A. Gibbs (US), Chao Hong (US), Xue-jie Yu (US), David H. Walker (US), and George M. Weinstock (US) sequenced the genome of R. typhi and found it to be nearly identical to its close relative R. prowazekii and highly similar to R. conorii and other bacteria of the spotted fever group. The high degree of similarity between R. typhi and R. prowazekii illustrates the small differences that can affect virulence in different hosts. Thus, despite their close genetic relatedness, R. prowazekii is highly pathogenic in humans, whereas R. typhi is a milder pathogen in humans (1019).


Isaac de La Peyrère (FR) wrote one of the first books to challenge the biblical account of creation. Based on human artifacts he asserted that Adam and Eve were the founding couple only of the Jews. The Gentiles were older—pre-Adam. His book became very popular—translated into several languages—and thus earned him the ire of both the Catholics and the Calvinists. His book was burned in Paris, he was forced to recant his ideas, then forced to live out his life in a convent (874).


Conrad Victor Schneider (DE) argued that the nasal mucosa, and not the ventricles or the brain, is the source of nasal secretions (1391).  He did not know that the racemose glands produce the nasal secretion.



Thomas Wharton (GB) discovered the duct of the submaxillary salivary gland (Wharton’s duct) and a gelatinous intercellular substance that is the primitive mucoid connective tissue of the umbilical cord (Wharton’s jelly). He also deserves credit for being the first to associate the adrenal glands with a function of the nervous system. His description of the adrenals taking a substance from nerves and transferring it to veins preceded the neuroendocrine concept of the adrenal medulla that we have only appreciated in the 20th century (1760).

Rudolf Albert von Kölliker (CH) confirmed Wharton’s work on the adrenal glands (1699).


Dominici de Marchettis; Domenico De Marchetti; Dominicus de Marchettis (IT) shows anastomosis of arterioles and veins by injection (419).

Étienne Blankaard; Steven Blankaart; Stephano Blancardo; Stephen Blancard; Blancardus (NL) demonstrated by injection, in 1675, the continuity of arterial and venous capillaries (153). See, Marello Malpighi (IT), 1661. Leonardo da Vinci (IT), in his dissections (1489–1515), injected the blood vessels with wax for preservation and thereby discovered and named the capillaries.



A pandemic of malarial fever (the ague) takes place.



England experiences epidemic catarrhal fever (probably influenza).



Boston, MA experienced a measles (rubeola) epidemic (1029).


Christopher Wren (GB) is credited with the creation of the first syringe for intravenous injections by fastening a dog’s bladder to a sharpened goose quill (597). Wren was preceded in 1652 in the use of this device by Francis Potter, a British rector, whose choice of pullets as an experimental animal doomed his experiments to failure (747; 841).

Johann Daniel Major (DE) and Johann S. Elsholtz (DE) wrote the first books on intravenous infusions in humans (495; 972).

Dominique Anel (FR), a surgeon to the seventeenth-century French army, is usually credited with the invention, in 1714, of the kind of syringe used today. He devised this instrument for the surgical treatment of fistula lacrymalis (1223).

Francis Rynd (IE) invented the hollow metal needle. He first used it in 1844 to administer morphine by gravity through the needle into a patient suffering from neuralgia (1336).

Charles-Gabriel Pravaz (FR) and Alexander Wood (GB) are independently credited with the invention of the hypodermic syringe in 1853. Pravaz, a veterinarian, made intra-arterial injections into animals to treat aneurysm (1216). Wood, a physician, first made subcutaneous injections of opiates to relieve pain (1793). The first recorded fatality from a hypodermic syringe induced overdose was Dr. Wood's wife. The tragedy arose because she was injecting morphine to excess.


The Academia del Cimento was founded at Florence, Italy. Its purpose was scientific investigation.



Thomas Willis (GB) tells of typhus and influenza being present in England. An outbreak of influenza in April 1658 led him to treat almost 1000 patients a week for a short period (1781).



James Ussher (GB) calculated the date of creation, based on the ages of biblical prophets. Using his calculations, future theologians identified the date of creation as October 26, 4004 B.C.E. (1582).


Jan Swammerdam (NL) discovered the erythrocyte in the frog (1658) then in man (1662), described lymphatic valves and the alteration in the shape of muscles during contraction. In his study of the insects he produced outstanding drawings, classified them, and described their transformations, i.e., he started modern entomology. Swammerdam’s work was unpublished until Herman Boerhaave (NL) published it at his own expense (1517; 1518). He is commemorated by Atylus swammerdami Milne-Edwards, 1830. Note: The 1737-1738 book is considered the finest one-man collection of microscopic observations.


Francois de la Boë Sylvius; Franciscus Sylvius (DE-NL) promoted the Iatro-chemical school of medicine, whose followers used medicines and did not accept the humoral pathology. While professor of medicine at Leyden he convinced the authorities to build a Laboratorium, probably the first chemical laboratory in a university. Sylvius introduced bedside teaching and stressed the importance of pathological studies. He pointed out that the formation of tubercles in the lungs represents the essential pathological finding in phthsis (tuberculosis) (1529; 1530).


Johann Jakob Wepfer (CH) described the autopsy of a case with subarachnoid hemorrhage and theorized that a broken blood vessel in the brain may cause apoplexy (stroke) (1753).



“In December 1659 the (until then unknown) Malady of Bladders in the Windpipe, invaded and removed many Children; by Opening of one of them the Malady and Remedy (too late for very many) were discovered.” (1003) Cotton Mather (US), minister in Boston, MA. Note: most likely a reference to diphtheria


Thomas Willis (GB) proposed the idea that fermentation is an internal motion of particles. He pointed to the similarity between fermentation and putrefaction. Early chemists were interested in putrefaction or rotting of various infusions because it was known that industrially useful substances such as lactic acid, butyric acid, or ethanol could be obtained from these infusions as they putrefied (1773).



The Royal Society of London took as its motto the phrase Nullius in verba [No man’s word shall be final].


Robert Boyle (GB) was convinced of the particulate nature of air. He explored not only the physical properties of air, but also its fundamental role in combustion and respiration, through the use of physiological experiments (187; 192).


Nicolas Le Febvre (FR), Thomas Jolly (FR), and Abbaye Saint-Denis (FR) wrote Traicte de la Chymie in which they held that the function of air in respiration was to purify the blood (902).


Konrad Victor Schneider (DE) demonstrated that nasal mucus is a product of mucous glands lining the nasal cavity (1392).



“By diligent investigation I have found the whole mass of the lungs, with the vessels going out of it attached, to be an aggregate of very light and very thin membranes, which, tense and sinuous, form an almost infinite number of orbicular vesicles and cavities, such as we see in the honey-comb alveoli of bees, formed of wax spread out into partitions. These [vesicles and cavities] have situations and connection as if there is an entrance into them from the trachea, directly from the one into the other; and at last they end in the containing membrane. …with greatest diligence I have been able to make out, those membranous vesicles seem to be formed out of the endings of the trachea, which goes away at the extremities and sides into ampulus cavities. …Seeing that the air which rushes from the trachea into the lungs requires a continuous path for easy and rapid ingress and egress, whence possible this internal tunic of the trachea, ends in sinuses and vesicles, makes a mass of vesicles like an imperfect sponge so to speak.” From De Pulmonibus Observationes Anatomicae by Marcello Malpighi (IT), here translated by J. Young (974; 984)

Note: His discovery of the capillary circulation was published in the form of two letters, ‘De Pulmonibus’, addressed to Giovanni Borelli (IT). Using frog dissection in 1661, Marcello Malpighi (IT) discovered and observed the capillaries in the frog’s lungs, he thus studied the movement of the blood in a contained system . He hypothesized that capillaries were the connection between arteries and veins that allowed blood to flow back to the heart in the circulation of the blood, as first asserted by William Harvey.


“The method of inoculation having been brought to light during my reign, I had it used upon you, my sons and daughters, and my descendants, and you all passed through the smallpox in the happiest possible manner…. In the beginning, when I had it tested on one or two people, some old women taxed me with extravagance, and spoke very strongly against inoculation. The courage which I summoned up to insist on its practice has saved the lives and health of millions of men. This is an extremely important thing, of which I am very proud.” Emperor F'ang (CN) (606).


Robert Boyle (GB) is credited with being the first to produce pure methyl alcohol (methanol, wood alcohol) despite the fact of its production in antiquity (188).


Robert Boyle (GB), in his book The Sceptical Chemist, is given credit for defining an element as it is currently used in chemistry. He also emphasized the importance of the Baconian method of experimental science as opposed to blind acceptance of previous authority (188).


Marcello Malpighi (IT), anatomist, general histologist, and professor of medicine, discovered fine hair-like blood vessels in the lungs of frogs connecting arterial and venous blood; they were later called capillaries. He offered proof that the windpipe terminates in many small, dilated air vessels; they were later called alveoli. Malpighi thus presented the correct anatomy for respiratory exchange. He described lymph nodes and discussed the glands (glomeruli) of the kidney. He wrote the first treatise to deal with an invertebrate—the silkworm. He was among the first to describe the embryonic development of the chick, using the microscope. (See, Highmore 1651b) He described the respiratory vessels in insects, spiral looking cells in plant stems, and openings on the underside of leaves; later to be called stomata, and gave the first account of the development of the seed (18; 974; 979; 980; 983; 986). He was commemorated with the plant genus Malpighia and the family, Malpighiaceae.


John Ray (GB) discovered hermaphroditism among pulmonate snails. In his book, Catalogus Plantarum Circa Cantabrigiam Nascentium he says, "Not even this lethal plant [the deadly nightshade (Atropa belladonna)] escapes the teeth of snails and slugs for its leaves are freely eaten in spring by these creatures. In passing one may mention that they are hermaphrodite. That they alternately function as male and female by impregnating and receiving at the same time will be clear to anyone who separates them as they are having intercourse in Spring, although neither Aristotle nor any other writer on Natural History has recorded this fact" (507; 1249).

Jan Swammerdam (NL), in his 1669 book, Historia Insectorum Generalis mentioned "Snails discharge their excrements by the neck, and are each of them, both Male and Female" (1514).

 Johann Jacob Harder (CH) discovered hermaphroditism among the pulmonate mollusks (672).


Thomas Willis (GB) suggested the nervous origins of convulsive disorders such as epilepsy, asthma, apoplexy, narcolepsy, and convulsive coughs. He gave an account of whooping cough, described the role of bronchial innervation, and the late-stage effects of syphilis on the brain. He describes a typhoid epidemic of 1661, in England (1775).


Thomas Willis (GB) in a section titled ‘Of the Phrensy’, offered ‘meningitis’ as the modern diagnosis of phrensy/phrenitis. Moreover, Willis clearly described the pathology of compression of the brain as a consequence of meningeal inflammation and also mentions an epidemic of meningitis, reigning An. 1661, which chiefly infested the brain and the genus nervosum (1780).


Kenelm Digby (GB), M.A. Hupka (), and Josephus Wolff () provided evidence of a skin graft rejection on a patient's nose in the year 1661 (453).


Scarlet fever appears in England.



The Royal Society of London was formally incorporated in 1662. It had begun in 1645 when a group of doctors and scientists in London formed a society they called The Invisible College. It briefly moved to Oxford then returned to London. Charles II approved their organization in 1660 (1466).


Robert Boyle (GB) formulated what became known as Boyle’s law—at a stated temperature, a given mass of gas varies in volume inversely as the pressure (189).


Niels Stensen; Nicholas Stenonis; Nicholas Steno; Nicolaus Steno; Niels Steensen; Nicolaus Steensen (DK) described the excretory duct of the parotid gland (parotis or (Stensen’s duct) while dissecting the head of a sheep. He also described the lacrymeal gland and ducts used to bath the eye (1482; 1487; 1492).


Smallpox (red plague) killed more than a thousand Iroquois in Central New York State (858).



The plague occurs in England.



Jan Swammerdam (NL) performed laboratory experiments on the contraction of frog muscle (1517; 1518).


Marcello Malpighi (IT) posthumously described tubular sense organs he found in some fish in 1663. These became known as "ampullae of Lorenzini" (982). See, Stefano Lorenzini, 1678.


Lorenzo Bellini (IT) described renal tubules for the first time, Bellini’s ducts, and proposed how urine might be formed (116).


Hendrick van Roonhuyse (NL) gave the first deliberate and detailed account of the repair of a vesicovaginal fistula. His book is regarded as the first work on operative gynecology in the modern sense. He successfully performed caesarean section several times, and he used retractors for the repair of vesico-vaginal fistulae (1645).


Girolamo Cardano; Jerome Cardan (IT) used raised letters to communicate with the blind and described a formal method for teaching deaf mutes to communicate with signs (263).


North American colonists established their first hospital. It was on Long Island in what would become New York State (973).



"They have considered the heart as the seat of vital heat, the throne of the spirit or the soul itself. They have revered the organ as sun or king, but if one looks at the heart with more care, only its muscular nature can be found" Niels Stensen; Nicholas Stenonis; Nicholas Steno; Nicolaus Steno; Niels Steensen; Nicolaus Steensen (1483)


Robert Boyle (GB), in 1664, was the first to distinguish between acids, bases, and neutral substances, and in his 1664 Experiments he codified the analysis of solutions by use of colored vegetable extracts serving as "indicators" of the presence of acids or bases or neutral substances (191). He is credited with the introduction of litmus paper.


William Croone; William Croune (GB) suggested that within muscle cells the globules (sarcomeres), delineated by cross-striations, may serve as units of contraction. He also assumed that contraction occurs without a change in muscle volume and proposed that nerves play a role in conducting the stimulus from the brain to the muscle fibers (332; 333). See, Stensen, 1664 and 1667.


Reijnier de Graaf (NL) performed the first cannulization. He introduced a temporary cannula, made of the quill of a wild duck, into the pancreatic duct of a living dog, and studied the properties of the liquid obtained. He noted its color, what he thought was an acid reaction, and its bitter taste (401; 405).


Gerard Blasius; Gerhard Bläes; Gerardus Leonardus Blasius (NL) discovered and named the arachnoid membrane, one of the three meninges covering the brain; presenting his finding to the Anatomical Society of Amsterdam in 1664 (154; 520).

Humphrey Ridley (GB) described the arachnoid membrane and observed that it invests various cerebral vessels and intracranial nerves. He disproved the idea that some cerebral arteries terminated directly into the major venous sinuses of the brain (1286).

Frederik Ruysch (NL) described the arachnoid membrane as a complete layer surrounding the brain (505).


Thomas Willis (GB) gave one of the earliest descriptions of the arterial supply of the brain, the Circle of Willis, and a precise account of the cranial nerves, Nerves of Willis. He was certain about the location of the thought process. He wrote, "in truth within the womb of the brain all the conceptions, ideas, forces and powers whatsoever both of the rational and sensitive soul are formed, and having there gotten a species are transformed into acts." Regarding the function of the cerebral cortex he said, "Then if the same fluctuation of the spirits is struck against the cortex of the brain, as its utmost banks, it impresses on it the image or character of the sensible object, which when it is afterwards reflected or bent back, raises up the memory of the same thing…And sometimes a certain sensible impression…striking against the cortex of the brain itself…and so induces memory with phantasie." For him the cerebellum and the pons were responsible for the involuntary motions of various organs, such as the heartbeat, breathing and gastrointestinal peristalsis. He was the first to describe the ganglions of the sympathetic nerves and recognized the vagus nerve, erroneously assuming it had its origin in the cerebellum. Domenico de Marchetti (IT) coined the name vagus for this cranial nerve.

Willis attempted to correlate the organization of the brain’s convolutions with intelligence and stressed that the brain's workings are mediated by the brain parenchyma and not, as previously held, by the ventricles.

He stressed that the nerves do not contain cavities like arteries and veins but are firm and compacted. Willis described the eleventh cranial nerve. In the 1664 work he coined the word neurology (neurologie) and named the pyramidal system in the brain (believing it to be a reservoir for the animal spirits). He anticipated what would later be called dementia praecox when in 1664 he wrote, "young persons who, lively and spirited, and at times even brilliant in their childhood, passed into obtuseness and hebetude during adolescence" (1774; 1778).

Emanuel Swedenborg (SE) deduced that the cerebrum of the brain is the source of understanding, thinking, judging, and willing. He inferred the intellectual functions of the frontal lobes. He described what is the first known anticipation of the neuron (a nerve cell with its processes) (14; 1522).


Niels Stensen; Nicholas Stenonis; Nicholas Steno; Nicolaus Steno; Niels Steensen; Nicolaus Steensen (DK) made a careful investigation of the ox heart musculature. After a thorough examination he stated: "As to the substance of the heart, I think I am able to prove that there exists nothing in the heart that is not found also in a muscle, and that there is nothing missing in the heart which one finds in a muscle." He also described the anatomy and function of the respiratory muscles including the diaphragm (1483; 1486; 1491).



Cromwell’s troops in Jamaica suffer from an epidemic of dysentery.



Robert Hooke (GB) published a theory of combustion. He stated that ordinary air contains a small amount of matter identical with a substance found in nitre (potassium nitrate). This substance has the property of rapidly dissolving combustibles, with combustion being the result of their rapid motion (764). In this same publication Hooke described and illustrated a parasitic rose rust (Phragmidium mucronatum) and a saprophytic Mucor.


Robert Hooke (GB) used a compound microscope to describe small pores in sections of cork that he called cells. " . . . I could exceedingly plainly perceive it to be all perforated and porous. . . these pores, or cells, . . . were indeed the first microscopical pores I ever saw, and perhaps, that were ever seen, for I had not met with any Writer or Person, that had made any mention of them before this." In his book, Micrographia, he also described and made beautiful drawings of insects, feathers, Foraminifera, and fish scales, as well as, hair and wool both in their natural condition and after dying. He may be the first to have stained objects for viewing. He specifically mentions using logwood (hematoxylin) to stain fluids (764).


Robert Boyle (GB) presented his method of fixing and preserving soft-bodied animal specimens in wine spirits (190).

Adolph Hannover (DK) introduced the technique of fixing tissue in chromic acid to improve its contrast during microscopic observation (670).

Heinrich Müller (DE) introduced potassium dichromate as a tissue fixative (1079).


Frederik Ruysch (NL) provided the first description of the valves of the lymphatics (1333).


Marcello Malpighi (IT), and Carlo Fracassati (IT) distinguished the outer layer of the tongue and the reticular mucous layer and isolated the taste buds. They demonstrated that the white matter of the nervous system was made of bundles of fibers, which connected the brain with the spinal cord (987).


Johann Sigismund Elsholtz (DE) made the first attempt at intravenous anesthesia (495).


The Great Plague (Yersinia pestis) of London killed at least 20 percent of the city's population, perhaps as many as 100,000 people (858). It is likely that the rhyme Ring a Ring o’ Roses originated at this time although it did not appear in print until 1881. Ring a ring o’ roses refers to the circular rosy rash that is an early symptom of the plague. A pocketful of posies refers to herbs people carried in their pockets, believing they offered protection. A-tishoo! A-tishoo!/ We all fall down, tells of the plague’s fatal sneeze, which preceded physical collapse; literally the victim fell down dead (626).


Philosophical Transactions of the Royal Society of London, the oldest scientific journal printed in the English-speaking world, was first published in England on 6 March 1665. Henry Oldenburg (DE) was founder and editor.


Le Journal des Savants was first published in France. This is the oldest scientific journal, first issue, 5 January 1665.



Smallpox (red plague) was reported in Europe.



Robert Hooke (GB), on 9 November, wrote the Fellows of the Royal Society in London that, "I did heretofore give this Illustrious Society [the Royal Society] an account of an Experiment I formerly tryed of keeping a Dog alive…by the Reciprocal blowing up of his Lungs with Bellowes, and they suffered to subside, for the space of an hour or more, after his Thorax had been so display'd [cut open], and his Aspera arteria [bronchus had been] cut off just below the Epiglottis, and bound upon the nose of the Bellows." (143; 765).


Richard Lower (GB) discovered that venous blood is converted from dark red to a bright red by contact with something in the air that he called the nitrous spirit. He injected venous blood into inflated lungs and noted that it became bright red. He suggested that the blood absorbed from the air a definite chemical substance necessary for life, and that this was, in fact, the chief function of the pulmonary circulation. When he ligated the heart’s nerve connections, it palpitated, quivered, and after a few days stopped beating. He guessed that the nerves carried a spirit from the storeroom of the cerebellum to the heart. He observed that ligation of the inferior vena cava gives rise to ascites. Lower followed the flow of digested nutriment from intestine to lacteals to lymphatics to blood and so to various parts of the body and demonstrated that phlegm originates in the nasal membranes and not in the brain as was thought. He noted that excess pressure from the pericardial fluid could cause the heart to stop beating (647; 945-947). Note: Richard Lower may have been the first to describe congestive heart failure. See, Konrad Victor Schneider, 1660.


Thomas Sydenham (GB) studied predisposing causes of diseases using a rational approach to treatment of disease. He contended that healing would better be promoted when the root cause of a disease could be found along with the laws governing the course of the disease and that the patient was best served when the physician tried to assist nature. He encouraged students to learn about disease at the bedside. Sydenham supported the Hippocratic idea of humoral pathology. He treated anemic patients with what he called steel tonic, made by steeping steel filings in cold Rhenish wine (this process resulted in the formation of ferrous potassium tartrate). He is to be given credit for demonstrating that iron is essential in the diet. He popularized the use of laudanum (alcoholic tincture of opium) in English medicine and advocated the use of Peruvian bark or Jesuit’s powder (quinine) as an antimalarial. Sydenham wrote outstanding descriptions of many diseases such as scarlet fever, measles, influenza, and gout; being one of the first to describe in detail the so-called Bell’s palsy, however he will be remembered for reporting the definite clinical entity known as St. Vitus Dance or chorea minor in 1686. " This is a kind of convulsion, which attacks boys and girls from the tenth year to the time of puberty. It first shows itself by limping or unsteadiness in one of the legs, which the patient drags. The hand cannot be steady for a moment. It passes from one position to another by a convulsive movement, however, much the patient may strive to the contrary." His description of measles is excellent, "The measles generally attacks children. On the first day they have chills and fever…On the second…cough…The nose and eyes run continually; and this is the surest sign of measles…[on] the fourth day…there appear on the face and forehead small red spots, very like the bites of fleas" (1524; 1526; 1527). Note: St. Vitus Dance or chorea minor is an infectious disease of the central nervous system, appearing after a streptococcal infection, with subsequent rheumatic fever, characterized by involuntary purposeless contractions of the muscles of the trunk and extremities.

Albert Delcourt (FR) and René Sand (FR) discovered that the pathophysiology of Sydenham’s chorea involves inflammation of both the cortex and the basal ganglia of the brain (439).

Frederick John Poynton (GB) and Alexander Paine (GB) determined that the causal agent of Sydenham’s chorea is a bacterium they named Diplococcus rheumaticus (1215).


Heinrich Meibom (DE) described and rediscovered the tarsal glands of the eyelid first noted by Julius Cesare Casserius (IT) in 1609 (270; 1027).


Marcello Malpighi (IT) described the glomeruli of the kidney, Malpighian bodies, as attached to the tips of arteries within the kidney. "The glands [i.e., the glomeruli] that have been discovered in the kidney…contribute a special service in the excretion of the urine…. They appear…spherical, precisely like fish eggs: and when a dark fluid is perfused through the arteries they grow dark." In this paper he also gives the first recorded description of Hodgkin’s lymphoma (975).


Marcello Malpighi (IT) noted in animals and humans the lobular structure of the liver, distinguishing the venous and biliary system. He suggested that bile was produced by the liver and not by gallbladder as thought previously (975).


Thomas Bartholin (DK) gave the first scholarly account of peasant immunization practices in Europe. He described how parents fearful for their children’s health, would seek out someone with a case of smallpox (red plague), preferably a mild one. The smallpox victim and the child would then make contact in such a way as to infect the child. After an incubation period of about a week the child, if it was lucky, would develop a mild case of smallpox and would emerge virtually unscarred and immune to the disease thereafter; the mild induced case gave the same protection that was provided by a severe one. Educated people came to call this practice of folk medicine inoculation (L. inoculare, to graft) or variolation (L. varus, pimple), Variola being the scholarly name for smallpox (83; 84).


A smallpox (red plague) outbreak struck Boston, but was relatively mild, and only about 40 people died (858).


The Académie des Sciences was founded in Paris.



Thomas Sydenham (GB) reports that smallpox (red plague) is present in England.



London experiences a smallpox (red plague) epidemic.



A pandemic of malarial fever (the ague) effects Europe.



Adrien Auzout (FR) and Jean Picard (FR) invented the type of micrometer that survived and is in use today (63).


Christopher Merrett (GB) publishes the first fauna of Great Britain, followed two years later by that of Walter Charleton (GB) (1033).


Niels Stensen; Nicholas Stenonis; Nicholas Steno; Nicolaus Steno; Niels Steensen; Nicolaus Steensen (DK) developed a mathematical description of muscular contraction, and attempted to show that muscles do not increase in volume during contraction. He dissected the head of a giant white shark and for the first time correctly identified the serpent tongues or tongue stones (glossopetrae) from the island of Malta as fossilized shark teeth. This was a significant event in early paleontology (1484; 1490; 1493).


Walter Needham (GB) gave the first thorough description of the placenta and the fetal membranes. He claimed, but did not prove, that the fetus in utero is nourished by blood from the placenta (1103).


Jan Swammerdam (NL) described docimasia of fetal lungs. This is a determination of whether air had entered the lungs of a dead infant, as an indication whether it was born dead or alive. He found that fetal lungs would float in water following respiration (1513).


An epidemic of plague at Nottingham marks a cessation of the disease in England.



Epidemic dysentery (the "bloody flux") is present in England (described by Sydenham and Morton).



A fatal aphthous fever (resembling thrush) is present in Leyden and other Dutch towns.



“We have no right to deny the entrance of air into the blood because, on account of the bluntness of our senses we cannot actually see the vessels by which it makes its entrance. . . . For in order that the aerea particles should mix with the mass of blood in a state of fine division and in a most intimate manner, it is necessary that they should enter the blood through channels or rather orifices, almost infinite in number, distributed here and there over the whole mass of the lungs.” John Mayow (GB) (1011).


Francesco Redi (IT) made many experiments to test the concept of spontaneous generation. He placed various kinds of flesh in open boxes and left them to decay. Maggots appeared, and he watched them become converted into adult insects. He also found ova which he considered had been dropped on the flesh by flies. He put a snake, some fish, some eels, and a slice of milk-fed veal into four wide-mouthed vessels, and sealed them with paper. He then prepared similar vessels in the same way except that they were left open. In the latter the flesh rapidly teemed with maggots but he could find none in the closed series, although here and there on the paper cover he saw maggots eagerly seeking any crevice through which they could penetrate to obtain food. He performed other experiments in which the paper was replaced by the finest gauze to allow airflow. He placed the gauze-covered vessels in a frame also covered by gauze. Maggots and flies were seen on the gauze but none appeared on the meat. He observed flies deposit their ova on the gauze. This was the first clear-cut case of using controls in a scientific experiment. By these experiments Redi destroyed the myth that maggots appear spontaneously on meat (246; 1257; 1260). It was Redi who introduced into the scientific method the serial procedure and comparison between research experiments and control experiments.


Reijnier de Graaf (NL) described the fine structure of the human testis and later the fine structure of the human ovary (whose name he suggested). He described the ovarian follicles (folliculus oophorus vesiculosus), which he mistakenly took to be the egg or ovum (402-404). In his honor, Albrecht von Haller (CH) was later to name the follicles on the surface Graafian follicles.

Karl Ernst von Baer (EE-DE-RU) discovered (in the dog) that the egg is a smaller body within the follicle and traced it to the uterus by way of the oviduct (1672-1675).


Niels Stensen; Nicholas Stenonis; Nicholas Steno; Nicolaus Steno; Niels Steensen; Nicolaus Steensen (DK), in 1668, discovered the fibrous nature of the nervous system’s white matter. This white matter he showed to consist of tracts of fibers in continuity with the nerves. He proposed that thought and movement depended on the arrangement and co-ordination of nerve fibers within the brain. This shattered the Greek theory that the ventricles were the principal functional elements of the brain and Descartes’ theory that the pineal gland was central to the thought process (1495).


L’Abbe Edmé Mariotte (FR) related his discovery of the blind spot of the eye in a letter to Christiaan Huygens (NL) then sent them to the Royal Society in London (997; 998).


Probably the earliest recorded epidemic of yellow fever to occur in non-tropical America, struck New York in late summer and early fall of 1668. It was described as an autumnal bilious fever in infectious form. The contemporary descriptions leave some possibility open that it could have been some other disease, but yellow fever seems the most likely (858).



England experiences dysentery (the "bloody flux") and infantile summer diarrhea (Thomas Sydenham and Thomas Willis).



“I first observed, that it is clearer than the light of noon, that man, like insects, is produced from a visible egg, which after being impregnated, is brought forth; that is, it is by local motion conveyed out of the ovary through a tube into the uterus which is the place wherein man, that rational animal, finds the first nourishment and represents as it were a Vermicle or Worm, or to use Harvey’s words, a Magot lying in the egg.” Jan Swammerdam (NL) (1515; 1517)

Although this statement does not conflict with the concept of preformation it is interesting because Swammerdam believed in preformation. See, William Harvey, 1651.


Hennig Brandt; Hennig Brand (DE) prepared white phosphorus by using the anaerobic destructive distillation of the solids of urine. Elemental phosphorus passed over and collected under the liquid in the retort. He wrote about his discovery to the mathematician and philosopher Gottfried Wilhelm Leibniz (DE), who later in his Historia Inventionis Phosphori (Berlin 1710), wrote that Brand was an impoverished merchant who sought to restore his wealth by converting base metals into gold; and during his alchemical experiments with urine discovered phosphorus. As was typical in alchemy at the time, the details of the method were kept secret. Brand sold his secret to the German physician Johannes Daniel Krafft (1594).


John Wray; John Ray (GB) reports experiments by Francis Jessop (GB), Samuel (GB), and John Fisher (GB) on the isolation of formic acid by the distillation of large numbers of ants (1796).

Andreas Sigismund Marggraf (DE) obtained formic acid by distilling ants with steam (994).

Théophile-Jules Pelouze (FR), an assistant of Joseph Louis Gay-Lussac (FR), in 1832, synthesized formic acid from hydrocyanic acid (1168).


Jan Swammerdam (NL) described water-fleas (Daphnia) (1514).


Jan Swammerdam (NL) described the metamorphosis of insects, supporting the preformation doctrine (1517; 1518).


John Mayow (GB)—who also gives a remarkably correct anatomical description of the mechanism of respiration – preceded Priestley and Lavoisier by a century in recognizing the existence of oxygen, under the guise of his spiritus nitro-aereus, as a separate entity distinct from the general mass of the air. Mayow perceived the part spiritus nitro-aereus plays in combustion and in increasing the weight of the calces (oxides) of metals as compared with metals themselves. Rejecting the common notions of his time that the use of breathing is to cool the heart or assist the passage of the blood from the right to the left side of the heart, or merely to agitate it, Mayow saw in inspiration a mechanism for introducing oxygen into the body, where it is consumed for the production of heat and muscular activity. He remarked, "The blood returning to the heart is for the greater part deprived of spiritus nitroaereus which it has left in the brain for the production of animal spirit." Mayow clearly points out that respiration within the fetus is possible because the placenta brings nourishment and spiritus nitro-aereus (oxygen) to it and reasons that the umbilical blood vessels near the shell of an egg bring spiritus nitro-aereus (oxygen) to the developing embryo. He even vaguely conceived of expiration as an excretory process (1011-1013). The 1669 tracts were presented in 1668. See, Hooke, 1665,


Marcello Malpighi (IT) produced the first monograph on an invertebrate, the silkworm. He dissected the silkworm under the microscope noting the air ducts (tracheae) and the blood duct with several pulsating centers (corcula). He also observed the heart, the gut, the glandular system now known as "Malpighian tubules", and the nerve chain (977).


Marcello Malpighi (IT) separated fibers from clotted blood free of red cells and serum and identified these using the single-lens microscope (976; 985).

William Hewson (GB) discovered that coagulable lymph (fibrinogen) is essential for blood clotting and that following sedimentation the coagulum property resides in the upper liquid part of the blood, above the red cells (730; 733).

Antoine Francois de Fourcroy (FR) and Louis Nicolas Vauquelin (FR) introduced the term fibrin. They demonstrated that plasma contained soluble substances, albumin and globulin, and that the precursor of fibrin was a soluble substance present in plasma but not in serum. The term globulin was used to describe the part of plasma precipitated when diluted in water, albumins remaining in solution (394)

Benjamin Guy Babington (GB) concluded that blood contains a soluble precursor to fibrin (fibrinogen) (64).

Andrew Buchanan (GB) concluded that coagulation of pleural, peritoneal, pericardial, serous testicular, and hydrocele fluids was not the result of the spontaneous coagulation of fibrin but rather that, …"like albumin and casein, fibrin often coagulates under the influence of suitable reagents: and that the blood and most other liquids of the body which appear to coagulate spontaneously, only do so in consequence of their containing at once fibrin and substances capable of reacting upon it and so occasioning coagulation." (241-244)

Rudolf Ludwig Karl Virchow (DE) formulated his postulates regarding clots in venous thrombosis (1665; 1667).

Rudolf Ludwig Karl Virchow (DE) was the first to use the term thrombin (1569).

Prosper Sylvain Denis (FR) published two monographs in 1856 and 1859 which validated and extended Panum’s technique of fractionating complex materials like egg albumin and blood plasma into distinct proteins by salting out. Upon the salting out of blood plasma it yielded a precipitate, which was not soluble in water but was soluble in a dilute salt solution. The salt soluble fraction possessed properties of a precursor to fibrin. Denis gave the name plasmine to this precursor of fibrin (441).

Benjamin Guy Babington (GB) had already named this fibrin precursor fibrinogen. See, Babington, 1830 above.

Hermann Adolf Alexander Schmidt (DE) separated plasmine into its two constituents, both proteids of the globulin class to which he gave the names fibrinogen and fibrino-plastic substance (1385). The later constituent was called para-globulin by Wilhelm Friedrich Kuhne (DE) and serum globulin by Theodor Weyl (DE) (870; 1759).

Hermann Adolf Alexander Schmidt (EE-DE) repeated the experiments described by Buchanan and called the activity fibrin ferment (thrombin). He found that fibrin ferment could be precipitated by addition of alcohol to fresh serum. Schmidt later concluded that since the presence of thrombin in the circulation did not allow blood to remain fluid it must have a precursor, prothrombin; at first, therefore, prothrombin was hypothetical. Prothrombin activation was thought to occur because of the presence of "zymoplastic substances" in the tissues (1386-1388). Note:

Olof Hammarsten (SE) noted that calcium chloride promoted coagulation and enhanced the amount of fibrin formed (665).

Olof Hammarsten (SE) and Karl Friedrich Wilhelm Ludwig (DE) showed that fibrinogen is the sole precursor of fibrin and that fibrin is the consequence of a reaction between thrombin and fibrinogen (666-668).

William Dobinson Halliburton (GB) concluded that coagulation of the blood is due to the formation of fibrin from fibrinogen which was previously dissolved in the blood-plasma; that this change is brought about by the fibrin ferment; and that the fibrin ferment is one of the products of the disintegration of the white blood-corpuscles that occurs when the blood is shed (662).

Joseph Lister (GB) maintained that the blood has no spontaneous tendency to clot but that it only clots when brought into contact with a foreign body (932).

Nicolas Maurice Arthus (FR), Calixte Pagès (FR), and M.L. Sabbatini (FR) observed that calcium precipitants inhibited coagulation, and that this effect was reversed when sufficient calcium was re‐added. Calcium was not required for the reaction of thrombin with fibrinogen, but was required for the conversion of the hypothetical prothrombin to thrombin (55; 1337).

Paul Morawitz (DE) synthesized various observations into one of the first formulations of the biochemistry of blood coagulation: prothrombin, he hypothesized, was converted into the enzyme thrombin by “thrombokinase” (tissue factor) in the presence of calcium; thrombin, in turn, converted fibrinogen to fibrin. Morawitz described four coagulation factors: fibrinogen (I), prothrombin (II), thrombokinase (III) and calcium (IV) and renamed Schmidt's zymoplastic substance thrombokinase (thromboplastin) (1063; 1064).

Pierre Nolf (FR) called this activity thromboplastic and used the term ‘tissue factor’ Nolf, 1908 #26183}.

William Henry Howell (US) later denominated them "tissue thromboplastins" (factor III) (773).

William Henry Howell (US) and L. Emmett Holt, Jr. (US) coined the term heparin to denote the presence of a fat-soluble anticoagulant in the liver. They also isolated a second fat-soluble anticoagulant they named pro-antithrombin (Gk. hepar) (774).

Lee M. Roderick (US) showed that "sw