Erythroblastosis fetalis due to rhesus incompatibility (Rh disease) between mother and child. With L. Burnham, E. M. Katzin, and P. Vogel.

Isolation of dicoumarol (3:3-methylene-bis-4-hydroxycoumarin). With C. F. Huebner.

Methemoglobinemia. Comly first suggested the above hypothesis, since proved valid.

Coombs’s test for detecting antibodies in various clinical scenarios, such as Rh disease and blood transfusion. With A. E. Mourant and R. R. Race. A fuller description appears in Brit. J. exp. Path.,1945, 26, 255-66.

Conglutination test.

Urethane in treatment of leukemia. With A. Haddow, I. Ap Thomas, and J. M. Watkinson.

Introduction of phenylindanedione.

Exchange transfusion.

Cause of hereditary methemoglobinemia elucidated.

Introduction of ethyl biscoumacetate (“tromexan”).

Christmas disease, hemophilia B, due to lack of Factor IX. Named after the patient whose case was the first recorded example. With six co-authors.

Synthesis of 6-mercaptopurine. 

In 1988 Gertrude Elion shared the Nobel Prize in Physiology or Medicine with George Hitchings and Sir James Black “for their discoveries of important principles for drug treatment.”

Clinical introduction of 6-mercaptopurine in treatment of acute leukemia and chronic myelocytic leukemia. With nine co-authors.

Introduction of myleran (busulphan). For results, see pp. 208-13.

With C. Zarafonetis, N. Smith, I. Woldow and D. C. H. Sun.

Clinical use of chlorambucil for chronic lymphatic leukemia. With L. G. Israels, J. D. N. Nabarro, and M. Till.

With J. G. Gorman and W. Pollack.

Cytosine arabinoside. With J. P. Holland, M. Weil, et al.

Epistle xxi, pp. 74-77, contains the first definite description of chlorosis. “De morbo virgineo”. English translation in No. 2241.

Classic description of chlorosis. Lange accurately diagnosed this condition, but it was left to Hoffmann to separate it as a definite entity. Hoffmann published his contribution to this subject in the thesis of his student Gottfried Emmrich.

First description of pernicious anemia. Paper read May 1, 1822.

For the treatment of chlorosis Blaud prescribed a pill (Blaud’s pill) composed of sulphate of iron and carbonate of potassium. Preliminary report in Bull. gén. Thérap.,1832, 2,154-55.

Foedisch showed chlorotic blood to be deficient in iron. See also Gaz. méd. Paris, 1837, 2 sér. 5,7.

Nasse gave the first clear description of anemia in pregnancy; he also noticed erythrocyte sedimentation in certain pathological conditions.

First description of pernicious anemia of pregnancy. Digital facsimile from the U.S. National Library of Medicine at this link.

Bennett described the anemia of pregnancy and defined it as resulting from the process of reproduction.

Addison included a classic description of pernicious (Addisonian) anemia in his papers on the condition later known as “Addison’s disease”. Although preceded by Combe, his account was more important in bringing the disease to the notice of the medical profession. See also No. 3864.

First reported case of (infantile) splenic anemia.

Duncan showed that the essential feature in chlorosis is a quantitative change in the hemoglobin content and not a great reduction in the number of red blood cells.

“Valsuani’s disease” – progressive anemia in pregnant and lactating women, probably first described by H. N. Bennett (No. 3117).

An important account of pernicious anemia of pregnancy.

In his account of progressive pernicious anemia, Biermer was first to describe the retinal haemorrhages. He was at one time accredited with the first description of pernicious anemia ; later it was shown that Addison had described the condition in his classic work on the suprarenals (No. 3118) and that Combe (No. 3112) had reported a case of pernicious anemia as far back as 1822. On the European Continent the condition is referred to as “Biermer’s disease”. Preliminary communication in Versammlung deutscherNaturforscher undAertze, 1868, Tageblatt No. 8, IX Sect., p. 173.

Pepper described bone-marrow changes of pernicious anemia, though his actual description more closely resembles leukaemia.

Cohnheim gave a more convincing account than Pepper of the bone-marrow changes in pernicious anemia.

First complete account of pernicious anemia. "In 1877, William Gardner and Osler described a patient who was almost certainly the first with the clinical, hematologic, and pathologic features to leave no doubt it was Addisonian pernicious anemia. 12 ^, 13 The case was that of a 52-year-old Englishman who complained of weakness and dyspnea on exertion, numbness of the fingers and the hands (difficulty buttoning his clothes), and a throbbing sensation in his temples. He died of progressive symptoms 3 months later. In the peripheral blood, Osler described macro-ovalocytes that measured up to 14 × 9 µ and large nucleated red cells with abnormal chromatin. At autopsy, pallor of the skin and organs was described, as well as a peculiar lemon tint to the skin and a thin gastric membrane. The bone marrow disclosed intense hyperplasia and was filled with large nucleated red cells having homogeneous stroma and finely granulated nuclei. This was the first clear description of the megaloblast so named by Paul Ehrlich 3 years later. Osler rejected William Pepper’s idea that PA was a form of pseudo-leukemia but hypothesized instead that it was a reversion of the bone marrow to an embryonic state, though why he did not know. Osler remarked it was “a disease … concerning the pathology of which we still have a good deal to learn, and concerning the successful treatment of which we as yet know nothing”  (Marvin J. Stone, "Diabetes mellitus and pernicious anemia: Interrelated therapeutic triumphs discovered shortly after William Osler’s death," Proc. (Baylor Univ. Med. Cent) 33 (2020) 689-692).

Comprehensive account.

In the above contributions to the knowledge of anemia, Ehrlich dealt in the first paper with the blood cells in anemia, and in the second gave the first description of the reticulocyte.

“Banti’s disease”. Banti described the pathological changes in the spleen in splenic anemia. A later paper in Sperimentale, 1894, 48, sez. biol., 407-32, gives an account of hepatic cirrhosis as the sequel of the earlier stage of splenic anemia; this sequel has been named “Banti’s syndrome”. A translation of this latter paper is in Medical Classics, 1937, 1, 901-27.

“Gaucher’s disease” – familial splenic anemia. Digital facsimile from wellcomecollection.org at this link.

First description of subacute combined degeneration of the spinal cord, which Leichtenstern termed progressive pernicious anemia in tabetics.

Ehrlich was first to distinguish the aplastic type of anemia.

Includes (pp. 614-751) an important account of chlorosis; Hayem, by his accurate observation, placed knowledge of the disease on a firm basis.

From this classic description of infantile pseudoleukemic anemia, the condition became known as “von Jaksch’s disease”.

Rindfleisch made the first clear statement of the bone marrow changes in pernicious anemia.

Bunge was father to the concept of iron-deficiency anemia.

Hereditary elliptocytosis.

Identification of the sickle-cell type of anemia.

"This case is reported because of the unusual blood findings, no duplicate of which I have ever seen described. Whether the blood picture represents merely a freakish poikilocytosis or is dependent on some peculiar physical or chemical condition of the blood, or is characteristic of some particular disease, I cannot at present answer. I report some details that may seem non-essential, thinking that if a similar blood condition is found in some other case a comparison of clinical conditions may help in solving the problem."

Simple achlorhydric (idiopathic microcytic) anemia described. Faber advanced the view that achylia gastrica was a cause both of pernicious anemia and of simple chlorotic anemia.

Four cases of pernicious anemia of pregnancy treated by blood transfusion.

Osler described his four-part classification of anemias of pregnancy: anemia from post-partum hemorrhage, severe anemia of pregnancy, post-partum anemia, and the acute anemia of post-partum sepsis. This was Osler's last substantial scientific publication; it appeared the year he died.

Mason gave sickle-cell anemia its present name.

First genetic study of sickling.

“Edelmann’s disease” – a type of chronic infectious anemia.

“Lederer’s anemia” first described.

These workers showed the beneficial effect of raw beef liver upon blood regeneration in anemia. Their work paved the way for the liver diet treatment of Minot and Murphy.

In 1934 Whipple shared the Nobel Prize in Physiology or Medicine with George R. Minot and William Parry Murphy "for their work on liver therapy for anemia."

Introduction of raw liver diet in the treatment of pernicious anemia. This treatment ranks as one of the greatest modern advances in therapy. See also the later paper in the same journal, 1927, 89,759-66. Reprinted in Blood, 1948, 3,8-21.

In 1934 Minot and Murphy shared the Nobel Prize in Physiology or Medicine with Whipple (see No. 3139) "for their work in liver therapy for anemia."

“Cooley’s erythroblastic anemia”, thalassemia. With E. R. Witwer and O. P. Lee. An earlier brief account by Cooley and Lee appeared in Trans. Amer. Pediat. Soc.,1925, 37, 29.

“Fanconi’s syndrome”, congenital hypoplasia of bone marrow with multiple congenital defects occurring as a familial disease.

Peabody studied the bone marrow in pernicious anemia. He suggested that failure of blood formation rather than hemolysis was the main defect in the disease, and that the benefit from liver feeding was due to a factor in liver that promoted development and differentiation of mature erythrocytes.

Castle showed pernicious anemia to be due to absence from the gastric juice of a substance (Castle’s intrinsic factor, hemopoietin) that reacts with an extrinsic factor present in many foodstuffs to form the anti-pernicious anemia factor. His experimental work resulted in the introduction of stomach preparations for the treatment of pernicious anemia. Preliminary communication in J. Clin. Invest., 1928, 6, 2.

Sturgis and Isaacs showed that stomach tissue contains a factor active in the treatment of pernicious anemia.

Gänsslen introduced an injectable liver extract in the treatment of pernicious anemia.

Wintrobe’s classification of the anemias.

First observations of hemopoietic effect of folic acid.

Davidson’s classification of the anemias.

Achrestic anemia described.

Whipple and Bradford contributed a classic paper on the pathology of thalassemia, a name introduced by them.

First evidence that thalassemia is genetically determined. Earlier report in Kliniki, Athens, 1936, 12, No. 5.

Hemopoietic properties of folic acid reported. With C. F. Vilter, M. B. Koch, and M. H. Caldwell.

Isolation, determination of structure, and final synthesis of folic acid.

First demonstration of the effectiveness of vitamin B12 in pernicious anemia.

First recognition, by Pauling and colleagues, of a structural hemoglobin variant, and the beginning of the molecular approach to disease. 

Genetic evidence that sickle-cell disease is inherited in a simple Mendelian manner.

Sickle-cell hemoglobin differs from normal hemoglobin by a single amino acid (valine for glutamic acid).

With R. Sephton Smith and R. M. Hardisty.

Explains the current distribution of sickling throughout the world.

Harveian Oration, 1928.

Covers the literature up to 1912. Reprinted in 2 vols, as Classics of cardiology, New York, Dover, 1961. Reprinted again, with volume 3 by John A. Callahan, Thomas E. Keys & Jack E. Key, Malabar, Florida, Krieger, 1983. Volume 4 by John A. Callahan, Dwight C. McGoon, and Jack D. Key, Malabar, Krieger, 1989. Vol. 3 covers literature from 1912 to 1955 in a style similar to the first 2 vols. Vol. 4 in 2 pts. covers material published up to 1975, with an abbreviated commentary. Part 1 of Vol. 4 covers cardiac surgery; part 2 covers cardiology.

Includes cardiovascular surgery.

Reprinted with new introduction by Joel D. Howell, San Francisco, Norman Publishing, 1990.

A scholarly work with extensive bibliographies.

Thirteen contributions edited by Boroviczény, H. Schipperges, and E. Seidler. Includes chronological table of events in the history of medicine and a bibliography.

Descriptions of 1112 items, many with very informative annotations by Bedford, who donated his collection to the Royal College of Physicians. In addition to his clinical and research work in cardiology Bedford was an exceptional scholar. His library was collected with deep understanding of the history of the subject, and annotated by Bedford with outstanding insight. It is indeed a classic among medical bibliographies.

A collective work by 19 authors, edited by M. M. Wintrobe. This is a detailed history of haematology, well documented and well indexed.

Translations of extensive selections from 19 famous and/or obscure works, with commentary and summary.

Aretaeus left many fine descriptions of disease; in fact Garrison ranks him second only to Hippocrates in this respect. In the printed editions of this bibliography, before the present online version, the Adams edition was cited no less than 12 times for individual diseases, plus its first citation in "Collected Works" (No. 22.) This number of citations is, of course, greater than any other specific work by any other author, though the number of citations may be a reflection of idiosyncracies of the compilers rather than a proportionate measure of the significance of Aretaeus in the history of medicine. The citations are as follows:

3162. On angina, or quinsey. In his Extant works, ed. F. Adams, 249-52, 404-07.

3163. On pleurisy. In his Extant works, ed. F. Adams, 255-58, 410-16.

2433. On elephas, or elephantiasis. In his Extant works, ed. by F. Adams, 366-73, 494-98. Classic description of “elephantiasis Aretaei”, nodous leprosy.

5046. On ulcerations about the tonsils. In hiis Extant works, ed. F. Adams, 253-55. Aretaeus’s description of ulcerations about the tonsils, which he called “ulcera Syrica”, clearly referred to diphtheria, of which it was the first unmistakable description. For his treatment of the disease, see pp. 409-10 of the same work.

5089. On dysentery. In his Extant works, ed. F. Adams. 353-57. Prior to Lösch’s discovery of E. histolytica, all forms of dysentery were differentiated only on clinical grounds.

4915. Extant works. Ed. F. Adams. Aretaeus wrote important accounts of melancholy (298-300, 473-78) and madness (301-04).

5146. On tetanus. In his Extant works, ed. F. Adams,  246-49, 400-04. Aretaeus left a full account of tetanus.

4484,  On arthritis and sciatica. In his Extant works, ed. by F. Adams,  362-65, 492-93,

3612. On jaundice, or icterus. In his Extant works, ed F. Adams, 324-28.

4510. On paralysis. In his Extant works, ed. F. Adams.

4808. On epilepsy, in his Extant works, ed F. Adams,  243, 296, 399, 468. Aretaeus was well acquainted with hemi-epilepsy from local injury in the opposite half of the brain; partly from this knowledge he formulated the “decussation in the form of the letter X” of the motor path. He first described epilepsy resulting from a depressed fracture of the skull. In his excellent description he made the first mention of the aura.

3925. On diabetes.In his Extant works, ed. F. Adams. 338-40, 485-86. The first accurate account of diabetes, to which Aretaeus gave its present name; he insisted on the part which thirst plays in the symptomatology. 

According to the Wikipedia article on Headache, Aretaeus also provied the first recorded classification system for headaches: "He made a distinction between three different types of headache: i) cephalalgia, by which he indicates a shortlasting, mild headache; ii) cephalea, referring to a chronic type of headache; and iii) heterocrania, a paroxysmal headache on one side of the head." 

Digital facsimile of Adams's Greek and Latin edition from the Internet Archive at this link.

Aretaeus left many fine descriptions of disease; in fact Garrison ranks him second only to Hippocrates in this respect. In the printed editions of this bibliography, before the present online version, the Adams edition was cited no less than 12 times for individual diseases, plus its first citation in "Collected Works" (No. 22.) This number of citations is, of course, greater than any other specific work by any other author, though the number of citations may be a reflection of idiosyncracies of the compilers rather than a proportionate measure of the significance of Aretaeus in the history of medicine. The citations are as follows:

3162. On angina, or quinsey. In his Extant works, ed. F. Adams, 249-52, 404-07.

3163. On pleurisy. In his Extant works, ed. F. Adams, 255-58, 410-16.

2433. On elephas, or elephantiasis. In his Extant works, ed. by F. Adams, 366-73, 494-98. Classic description of “elephantiasis Aretaei”, nodous leprosy.

5046. On ulcerations about the tonsils. In hiis Extant works, ed. F. Adams, 253-55. Aretaeus’s description of ulcerations about the tonsils, which he called “ulcera Syrica”, clearly referred to diphtheria, of which it was the first unmistakable description. For his treatment of the disease, see pp. 409-10 of the same work.

5089. On dysentery. In his Extant works, ed. F. Adams. 353-57. Prior to Lösch’s discovery of E. histolytica, all forms of dysentery were differentiated only on clinical grounds.

4915. Extant works. Ed. F. Adams. Aretaeus wrote important accounts of melancholy (298-300, 473-78) and madness (301-04).

5146. On tetanus. In his Extant works, ed. F. Adams,  246-49, 400-04. Aretaeus left a full account of tetanus.

4484,  On arthritis and sciatica. In his Extant works, ed. by F. Adams,  362-65, 492-93,

3612. On jaundice, or icterus. In his Extant works, ed F. Adams, 324-28.

4510. On paralysis. In his Extant works, ed. F. Adams.

4808. On epilepsy, in his Extant works, ed F. Adams,  243, 296, 399, 468. Aretaeus was well acquainted with hemi-epilepsy from local injury in the opposite half of the brain; partly from this knowledge he formulated the “decussation in the form of the letter X” of the motor path. He first described epilepsy resulting from a depressed fracture of the skull. In his excellent description he made the first mention of the aura.

3925. On diabetes.In his Extant works, ed. F. Adams. 338-40, 485-86. The first accurate account of diabetes, to which Aretaeus gave its present name; he insisted on the part which thirst plays in the symptomatology. 

According to the Wikipedia article on Headache, Aretaeus also provied the first recorded classification system for headaches: "He made a distinction between three different types of headache: i) cephalalgia, by which he indicates a shortlasting, mild headache; ii) cephalea, referring to a chronic type of headache; and iii) heterocrania, a paroxysmal headache on one side of the head." 

Digital facsimile of Adams's Greek and Latin edition from the Internet Archive at this link.

Vesalius’s consilium to Ingrassia, dated Madrid, 1562, in which he clearly described the operation for empyema (pp. 92-98). Although treatment of empyema by surgery was referred to in classical times, it became unfashionable, and Vesalius seems to have been the first to revive the actual use of surgery for this illness. English translation in O’Malley, Andreas Vesalius of Brussels, Berkeley, Univ. of California Press, 1965, pp.398-402.

The only complete edition of Willis's works in English, translated by the poet Samuel Pordage. It contains the translations of all his works except his Affectionum quae dicuntur hystericae (1671). The collection includes the First Edition in English of Willis's De anima brutorum. The volume is divided into six separately paginated sections, each with its own title-leaf. Included are English versions of Willis's three great works on the brain--Cerebri anatome, Pathologiae cerebri and De anima brutorum--as well as his clinical and pharmaceutical treatises. In Treatise III, pp. 128-158 Willis’s described the intercostal and spinal nerves. He described the ganglion chain as the “intercostal nerve” and thought it came from the head.

In addition to his invaluable work in the anatomy and physiology of the nervous system, Willis was the first to distinguish true diabetes mellitus, and showed that the polyuria was not due to any disease of the kidneys. He anticipated the recognition of hormones in the circulation of his suggestion that the phenomena of puberty were due to a ferment distributed through the body from the genitals. He discovered the superficial lymphatics of the lungs, distinguished acute tuberculosis from the chronic fibroid type and gave the first clinical and pathological account of emphysema.  The modern treatment of asthma really begins with Willis, who considered it to be of nervous origin. ("Of the convulsive cough and asthma," Treatise VIII, pp. 92-96; No. 3165). Willis was probably the first to report an epidemic of cerebrospinal fever" ("A description of an epidemical feaver, Treatise VIII, pp. 46-54; No. 4673). Transcription of the complete text from Early English Books Online at this link.

Floyer provided the first clear descriptions of cases of bronchial asthma. Floyer himself suffered from asthma for over 30 years. He recognized the influence of heredity in asthma. The above includes (p. 239) an important early account of emphysema, from a post mortem on a broken-winded horse.

Probably the earliest comprehensive clinical and pathological account of emphysema.

Includes Millar’s original description of laryngismus stridulus (“Millar’s asthma”).

First clinical description of chronic obstructive pulmonary emphysema. The lung on which Baillie performed an autopsy before describing this condition is said to have been that of Samuel Johnson. P. 46: Baillie suggested a relationship between rheumatic fever and valvular heart disease. See also Nos. 2281, 3218, & 3427.

Badham distinguished acute and chronic bronchitis from pneumonia and pleurisy, with which it had previously been confused. He gave the disease its present name. Digital facsimile from Google Books at this link.

Bowditch pioneered the operation for removal of pleural effusions with trocar and a suction pump devised by Morrill Wyman (1812-1903). See Bowditch’s earlier paper on the subject in the same journal volume, pp. 103-05.

First description of pulmonary aspergillosis.

The best work on asthma to appear during the 19th century. Salter, who had suffered from asthma from childhood, may be considered the first modern student of the condition. He called special attention to asthma from animal emanations (cats, rabbits, horses, dogs, cattle, etc.).

Hewett introduced a method of continuous aspiration of the thorax for emphysema.

Probably the earliest record of pneumococcus. Parrot reported the discovery made by Louis Pasteur.

In the same year as Pasteur, and independently, Sternberg discovered the pneumococcus (Streptococcus pneumoniae) demonstrating its carriage in the healthy human mouth.

Isolation of Klebsiella pneumoniae (“Friedländer bacillus”), which Friedländer regarded as the causal organism in all cases of lobar pneumonia.

Resection of portion of a lobe that was invaded by sarcoma of the rib.

Fraenkel showed definitely that the organism found by Pasteur (No. 3172) and Sternberg (No. 3173) was a cause of pneumonia.

Weichselbaum definitely established that Friedländer’s bacillus was responsible for pneumonia in a small percentage of cases.

First thoracotomy for empyema.

Schede introduced the method of extensive rib resection for the treatment of empyema.

Old antipneumococcal serum.

First thoracoplasty.

The procedure of decortication of the lung for treatment of chronic empyema was introduced by Delorme. For his later work on the subject, see Congr. franç. Chir., 1896, 10, 379.

Talcosis of lung reported.

Discovery of the causal organism of bovine pleuropneumonia, also known as lung plague. Nocard and Roux considered it a filterable virus but now known to be a mycoplasma.

“Grocco’s triangle”. Grocco described paravertebral dullness on the opposite side in pleural effusion.

Sauerbruch’s negative pressure chamber for the prevention of pneumothorax.

Introduction of therapeutic bronchoscopy, for treatment of asthma.

Körte was the first successfully to remove bronchiectatic lobes.

William Pasteur discovered and described massive collapse of the lung.

Jacobaeus adapted the cystoscope for the study of the interior of the body; this led to the introduction of the thoracoscope.

New antipneumococcus serum.

Tuffier’s method of extrapleural pneumolysis.

Digital facsimile from the Internet Archive at this link.

Dochez and Gillespie differentiated four types of pneumococci.

Kruse reported that colds could be produced in volunteers by intranasal instillation of bacteria-free filtrates of secretions from persons suffering from colds.

“Castellani’s bronchitis” (bronchospirochetosis).

First reported case.

Experimental introduction of iodoform (lipiodol) into the bronchial tree in dogs, obtaining satisfactory bronchograms. 

Abridged English translation, Baltimore, 1937.

Carcinoma of pharynx cured by the Coutard method of Röntgen therapy.

Important studies on bronchiectasis were carried out by Lynah and Stewart.

Laboratory demonstration of the antispasmodic action of theophylline on bronchial smooth muscle.

Hirsch established the value of theophylline in the management of asthma.

Heidelberger, Avery, and their colleagues made a chemical study of the antigenic constituents of the pneumococcus, separating the polysaccharide antigens.

Bronchography was advanced by the work of Sicard and Forestier on the intratracheal introduction of lipiodol.