Evarts Ambrose Graham (1883-1957), doyen of pulmonary surgeons.

Evarts Graham performed the first successful pneumonectomy in 1933. Evarts Ambrose Graham, the son of a Scotch Irish surgeon, was born on 19 March 1883. After early schooling in Chicago, he graduated at Princeton and returned to Chicago to study Medicine, taking his MD at Rush Medical College in 1907. The chemical aspects of pathological changes then occupied him fully until 1919, when he was appointed full-time professor of surgery at the Washington School of Medicine in St Louis. Visualisation of gallstones temporarily took his attention, but bronchogenic carcinoma was seldom far from his thoughts, and he recognised (too late to save himself) the causative association with cigarette smoking by 1950. He died on 4 March 1957.

Franciscus Cornelis Donders (1818-1889).

Franciscus Cornelis Donders was educated at Duizel and Boxmeer before entering the Military Medical School and the medical faculty at Utrecht University in 1835. In 1840, he received his MD from Leiden and spent 2 years in practice at Vlissingen before returning to Utrecht, where he was appointed as an extraordinary professor to lecture on forensic medicine, anthropology, general biology and ophthalmology. Refraction by the eye is complex, since the ray of light passes through many changes of refractive index in its path, and Donders simplified the account of the process by establishing an equivalent refractive system: the reduced eye. When Donders opened an Eye Hospital in 1858, he devoted himself to clinical ophthalmology, making fundamental advances in providing spectacles to correct errors of refraction-which he separated from errors of accommodation. In 1862, Donders was promoted as an ordinary professor at Utrecht and he handed over the greater part of his practice to his pupil Hermann Snellen. From narrow specialisation, Donders was freed to return to the broader physiology; subatmospheric pressure in the pleura was for a while referred to as 'Donders' pressure'; he also devised a method of measuring the mental reaction time taken in making discrimination, rather than the simple reaction time in which no choice is involved. He was widely honoured, presiding at international congresses, and elected as a foreign member of the Royal Society. He died suddenly on 14 March 1889, but his work lives on.

Robert Whytt (1714-1766): from dropsy in the brain to tuberculous meningitis.

Robert Whytt was born and educated in Edinburgh and served the City in the Royal Infirmary. A prolific author, his major work is usually said to be his Essay on the Vital and other Involuntary Movements of Animals (1751), based on his belief that a 'sentient principle' was not limited to the nervous system but was distributed throughout the body, a view that brought him into conflict with Albrecht von Haller, who held that the sentient and motor powers of the body were those of a machine. Whatever about the speculative nature of the sentient principle, Whytt was a clinician blessed with unusual clarity, and he is remembered today for his Observations on the Dropsy in the Brain (1768). Therein he described the clinical signs and symptoms of what later came to be recognised as tuberculous meningitis, the acute disease which appears early in the haemic spread of the infection in a child, and which was fatal until the discovery of chemotherapy and antimicrobials. John Cheyne, in describing two terminal cases, recognised the connexion between hydrocephalus and scrophula, and Dorothy Price provided a precise guide to the clinical picture in 1942. When streptomycin became available Christopher McSweeney used it to alter the bleak picture in Dublin, and was helped by the prevention resulting from neonatal BCG immunisation. Later antimicrobials have facilitated the avoidance of emergent bacillary resistance.

Claude Bernard and his revelations in physiology.

It was in Saint-Julien near Villefranche that Claude Bernard was born on 12 July 1813. About 20 years later he moved to Paris to become a dramatist but was directed into the study of medicine, the service at the Hôtel Dieu of Magendie that led him to the Collège de France. He entered Magendie's laboratory as a voluntary assistant and within a year became official préparateur. His early work on the chorda tympani and his MD thesis on gastric juice in 1843 set him on his lifelong discoveries in physiology. The central role of hepatic glycogenesis in the formation of sugar in animals was established around 1850, and he proceeded to show that section of the cervical fibres of the sympathetic chain led to congestion and increased temperature on that side of the face-resulting from paralysis of the vasomotor nerves. And there were vasodilator as well as vasoconstrictor fibres. After the salivary glands, the pancreas caught his attention and he discovered its ability to emulsify fatty material. Toxic and therapeutic substances were analysed: carbon monoxide paralyses carriage of oxygen by taking its place on haemoglobin; and curare abolishes voluntary movement by paralysis at the motor end-plate. But Bernard was above all a general physiologist, exemplified in 1872 and 1873 in his Lectures on the phenomena of life common to animals and plants, summarised in the aperçu 'the constancy of the internal environment is the condition of the free and independent life'. Claude Bernard died on Sunday 10 February 1878 in Paris.

First ladies in laying the foundation of neuroendocrinology.

Although women were welcomed into medical practice in increasing numbers by the close of the nineteenth century, it was not until the second quarter of the twentieth century that they were recognised as valuable collaborators and contributors in the nascent field of neuroendocrinology, wherein they soon made advances that have stood the test of time. Mary Pickford at Edinburgh measured the action of acetyl choline in the supraoptic nucleus of the hypothalamus and helped to establish that vasopressin and oxytocin are formed in separate and distinct neurons. Berta Scharrer, like her future husband Ernest Scharrer, was born in Munich. Their great contribution was the proof that the posterior pituitary is not a gland, but the location of the release into the circulation of vasopressin and oxytocin from fibres in the hypothalamico-hypophysial tract. Their work succeeded in establishing against high-powered, vehement opposition the value of histological evidence in elucidating synthesis, storage and release of secretion from neuro-endocrine cells. A Rockefeller travelling fellowship allowed Marthe Vogt to move from Berlin in 1932 to London and then to Cambridge. The relations between the cortex and medulla of the suprarenal gland and the control of adrenocorticotropin were her main concerns. Dora Jacobsohn emigrated to Sweden after graduating in Berlin in 1934. She investigated control of the anterior pituitary gland by the hypothalamus, and co-operated with Geoffrey Harris in establishing the role of the hypothalamico-hypophysial portal venous system that conveys the releasing factors that preside over anterior pituitary cells. Laboratory discoveries do not constitute the whole of science, for the interpretation of evidence and recognition of general principles deserve attention. Dorothy Price, from Aurora, Illinois, received her BS in 1922 at the University of Chicago, and was glad to find employment as a histology technician in the zoology laboratory, where she was quietly appropriated by Carl Moore (1892-1955), an investigator seeking the key to hormonal control of gonadal function. The burning question was the part played by what was (then) called hormone antagonism in the biology of the testis. Price recognised that the common factor in explaining the deleterious effects of oestrin and testosterone on the testes could be traced to the anterior pituitary: the pituitary controlled testicular secretion, and the male hormone in turn controlled gonadotropin release in the pituitary. This seesaw balance explained the problem, and was the first of many regulatory systems to be recognised as ensuring stability--and later became known as negative feedback. The contributions of these five women helped place neuro-endocrinology on a firm foundation for its later expansion.

Allvar Gullstrand and the slit lamp 1911.

The Swedish ophthalmologist and self-taught mathematician Allvar Gullstrand (1862-1930) invented the slit lamp to illuminate the anterior of the eye. With its rectangular beam of very bright light, he studied the structure of the cornea and the function of the lens. His dioptric investigations showed that, as well as the extracapsular mechanism described by Helmholtz, changes in the substance of the lens, that he termed intracapsular, also contribute to accommodation. However, his invention has been appropriated by clinical ophthalmologists and is now routinely used in examination of the eye.

William Wilde and the early records of consumption in Ireland.

Absence of documentary or bony evidence before the seventeenth century in Ireland is not conclusive evidence of freedom from tuberculosis. Clear records begin with Bills of Mortality kept in Dublin, the city at the centre of English administration of Ireland, and they show that the basis for an epidemic was firmly established therein before 1700. In the middle of the nineteenth century the cataclysmic Famine opened the floodgates of poverty and urban overcrowding that resulted in an alarming death rate that continued to increase until the early years of the twentieth century. It is to William Wilde (1815-1876) we owe the nuanced investigation of the earliest numerical records of consumption and related disorders in Ireland.

Jonathan Osborne (1794-1864) and his recognition of conduction aphasia in 1834.

In 1833 an accomplished 26-year-old linguist suffered a non-paralytic stroke. After he recovered, though he could utter a variety of syllables with ease, he spoke an unintelligible jargon that caused him to be mistaken as a foreigner. He was examined repeatedly over the course of a year by Jonathan Osborne (1794-1864), a Dublin physician and professor of materia medica, who found that the patient understood whatever was said to him, that he could read and write fluently, but had difficulty repeating words read to him or in reading aloud. Osborne recommended that he learn to speak English, his natural language, de novo and over 8 months measured his considerable improvement. To explain the patient's singular difficulty in repeating spoken words Osborne argued it was 'highly probable that, having been conversant with five languages, the muscular apparatus ranged among them, forming a kind of polyglot jargon [that was] wholly unintelligible' and the patient was 'unable to penetrate into and select the contents of the store according as the [words] were required'. The discrepancy between comprehension and repetition was later termed conduction aphasia.

Douglas Argyll Robertson (1837-1909) and his pupil.

Douglas Argyll Robertson's (1837-1909) experimental work with physostigmine in 1863 sharpened his knowledge of the innervation of the internal muscles of the eye. So he was ideally prepared in 1869 to analyse the conundrum when he saw patients with spinal cord disease who had lost the response to light even though accommodation to near objects was normal. By translating his knowledge of basic science to a clinical problem he drew attention to this phenomenon, known subsequently as the Argyll Robertson pupil that came to be considered pathognomonic of tabes dorsalis, general paresis and neurovascular syphilis.