Sir Henry Hallett Dale OM GBE PRS (9 June 1875 – 23 July 1968) was an English pharmacologist and physiologist. For his study of acetylcholine as agent in the chemical transmission of nerve impulses (neurotransmission) he shared the 1936 Nobel Prize in Physiology or Medicine with Otto Loewi.
Sir Henry Dale
Henry Hallett Dale
9 June 1875
|Died||23 July 1968 (aged 93)|
Henry Hallett Dale was born in Islington, London, to Charles James Dale, a pottery manufacturer from Staffordshire, and his wife, Frances Anne Hallett, daughter of a furniture manufacturer. Henry was the third of seven children, one of whom (his younger brother, Benjamin Dale) became an accomplished composer and warden of the Royal Academy of Music. Henry was educated at the local Tollington Park College and then The Leys School Cambridge (one of the school's houses is named after him) and in 1894 entered Trinity College, Cambridge, working under the physiologist John Langley. For a few months in 1903 he also studied under Paul Ehrlich in Frankfurt, Germany. Also in 1903, Dale assisted Ernest Starling and William Bayliss in the vivisection of a dog, by removing the dog's pancreas and then killing the dog with a knife, which ultimately led to the events of the Brown Dog affair. Dale received his Doctor of Medicine degree from Cambridge in 1909.
While working at the University College London, he met and became friends with Otto Loewi. Dale became the Director of the Department of Biochemistry and Pharmacology at the National Institute for Medical Research in London in 1914. He became a Fullerian Professor of Chemistry at the Royal Institution in 1942. During World War II he served on the Scientific Advisory Panel to the Cabinet.
Although Dale and his colleagues first identified acetylcholine in 1914 as a possible neurotransmitter, Loewi showed its importance in the nervous system. The two men shared the 1936 Nobel Prize for Medicine.
During the 1940s Dale was embroiled in the scientific debate over the nature of signaling at the synapse. Dale and others believed that signaling at the synapse was chemical, while John Carew Eccles and others believed that the synapse was electrical. It was later found that most synaptic signalling is chemical, but there are some synapses that are electrical.
Dale also originated the scheme used to differentiate neurons according to the neurotransmitters they release. Thus, neurons releasing noradrenaline (known in the United States as norepinephrine) are called noradrenergic, neurons releasing GABA are GABAergic, and so on. This is called Dale's principle (sometimes erroneously referred to as Dale's Law), one interpretation of which holds that each neuron releases only one type of neurotransmitter. This particular interpretation of Dale's principle has been shown to be false, as many neurons release neuropeptides and amino acids in addition to classical neurotransmitters such as acetylcholine or biogenic amines (see cotransmission) (Bear, et al. 2001). This finding, that numerous neurotransmitters can be released by the same neuron, is referred to as the "coexistence principle." This phenomenon was most popularized by the Swedish neuroanatomist and neuropharmacologist Tomas Hökfelt, who is considered to be the "Father of the Coexistence Principle."
Dale was elected a Fellow of the Royal Society (FRS) in 1914. He was knighted in 1932, receiving the Knight Grand Cross of the Order of the British Empire in 1943 and the Order of Merit in 1944. He served as President of the Royal Society from 1940 to 1945 and President of the Royal Society of Medicine from 1948 to 1950. The Sir Henry Dale Fellowships of the Wellcome Trust are named in his honour and the Society for Endocrinology awards the Dale Medal annually in his honour.
In 1904, Dale had married his first cousin Elen Harriet Hallett and had a son and two daughters. One of their daughters, Alison Sarah Dale, married Alexander R. Todd, who too won the Nobel Prize and served as President of the Royal Society from 1940 to 1945.
The year 1936 in science and technology involved some significant events, listed below.Dale's principle
In neuroscience, Dale's principle (or Dale's law) is a rule attributed to the English neuroscientist Henry Hallett Dale. The principle basically states that a neuron performs the same chemical action at all of its synaptic connections to other cells, regardless of the identity of the target cell. However, there has been disagreement about the precise wording.
Because of an ambiguity in the original statement, there are actually two versions of the principle, one that has been shown definitively to be false, and another that remains a valuable rule of thumb. The term "Dale's Principle" was first used by Sir John Eccles in 1954, in a passage reading, "In conformity with Dale's principle (1934, 1952) that the same chemical transmitter is released from all the synaptic terminals of a neurone…" Some modern writers have understood the principle to state that neurons release one and only one transmitter at all of their synapses, which is false. Others, including Eccles himself in later publications, have taken it to mean that neurons release the same set of transmitters at all of their synapses.
Dale himself never stated his "principle" in an explicit form. The source that Eccles referred to was a lecture published by Dale in 1934, called Pharmacology and nerve endings, describing some of the early research into the physiology of neurotransmission. At that time, only two chemical transmitters were known, acetylcholine and noradrenaline (then thought to be adrenaline). In the peripheral nervous system, cholinergic and adrenergic transmission were known to arise from different groups of nerve fibers. Dale was interested in the possibility that a neuron releasing one of these chemicals in the periphery might also release the same chemical at central synapses. He wrote:
It is to be noted, further, that in the cases for which direct evidence is already available, the phenomena of regeneration appear to indicate that the nature of the chemical function, whether cholinergic or adrenergic, is characteristic for each particular neurone, and unchangeable.
And near the end of the paper:
When we are dealing with two different endings of the same sensory neurone, the one peripheral and concerned with vasodilatation and the other at a central synapse, can we suppose that the discovery and identification of a chemical transmitter of axon-reflex vasodilatation would furnish a hint as to the nature of the transmission process at a central synapse? The possibility has at least some value as a stimulus to further experiment.
With only two transmitter chemicals known to exist at the time, the possibility of a neuron releasing more than one transmitter at a single synapse did not enter anybody's mind, and so no care was taken to frame hypotheses in a way that took this possibility into account. The resulting ambiguity in the initial statements led to some confusion in the literature about the precise meaning of the principle. Nicoll and Malenka, for example, understood it to state that a neuron always releases one and only one neurotransmitter at all of its synapses. In this form it is certainly false. Many neurons release more than one neurotransmitter, in what is called "cotransmission". Although there were earlier hints, the first formal proposal of this discovery did not come until 1976. Most neurons release several different chemical messengers. In modern neuroscience, neurons are often classified by their neurotransmitter and most important cotransmitter, for example striatal GABA neurons utilize either opioid peptides or substance P as the primary cotransmitter.
In a 1976 publication, however, Eccles interpreted the principle in a subtly different way:
"I proposed that Dale’s Principle be defined as stating that at all the axonal branches of a neurone, there was liberation of the same transmitter substance or substances."
The addition of "or substances" is critical. With this change, the principle allows for the possibility of neurons releasing more than one transmitter, and only asserts that the same set are released at all synapses. In this form, it continues to be an important rule of thumb, with only a few known exceptions, including David Sulzer and Stephen Rayport's finding that dopamine neurons also release glutamate as a neurotransmitter, but at separate release sites.David Innes Williams
Sir David Innes Williams (12 June 1919 – 3 May 2013) was a British paediatric urologist.Department of Physiology, Development and Neuroscience, University of Cambridge
The Department of Physiology, Development and Neuroscience, (PDN) is a part of the School of Biological Sciences at the University of Cambridge. Research in PDN focuses on three main areas: Cellular and Systems Physiology, Developmental and Reproductive Biology, and Neuroscience and is currently headed by Sarah Bray and William Colledge. The department was formed on 1 January 2006, within the School of Biological Sciences at the University of Cambridge from the merger of the Departments of Anatomy and Physiology. The department hosts the Centre for Trophoblast Research and has links with the Cambridge Centre for Brain Repair, the Cambridge Stem Cell Institute, and the Gurdon Institute.Director of the Royal Institution
Below are directors of the Royal Institution of Great Britain, with date of appointment.
Director of the Laboratory1801 Humphry Davy
1825 Michael Faraday
1867 John Tyndall
1887 James DewarDirector of the Davy-Faraday Research Laboratory1896 James Dewar
1896 Lord Rayleigh
1923 William Bragg
1942 Henry Hallett Dale
1946 Eric Rideal
1950 Edward Andrade
1954 Lawrence Bragg
1998 Richard Catlow
2008 Quentin PankhurstDirector1965 William Lawrence Bragg
1966 George, Baron Porter of Luddenham
1986 David Philips (acting)
1986 John Meurig Thomas
1991 Peter Day
1998 Susan Adele, Baroness Greenfield of Ot Moor
2017 Sarah Harper
2018 Shaun FitzgeraldHector MacLennan
Sir Hector MacLennan FRCP FRCPGlas FRCOG (1 November 1905 – 6 January 1978) was a Scottish gynaecologist, knighted in the 1965 Birthday Honours.He was President of the Royal Society of Medicine from 1967 to 1969.
His son is Robert Maclennan, Baron Maclennan of Rogart.Henry Dale
Henry Dale may refer to:
Henry Hallett Dale (1875–1968), English pharmacologist and physiologist
Henry Dale (MP) for BristolJohn Vivian Dacie
Sir John Vivian Dacie, FRS (20 July 1912 Putney, London – 12 February 2005) was a British haematologist.List of Fellows of the Royal Society elected in 1914
This is a complete list of Fellows of the Royal Society elected in 1914. There were no foreign members elected this year.List of Nobel laureates affiliated with University College London
University College London (UCL) is one of the two founding colleges of the University of London. There have been 33 Nobel Prize laureates amongst UCL’s alumni and current and former staff. UCL has the most Nobel affiliations among colleges and schools of the University of London, which has produced as many as 72 Nobelists till 2010.List of Presidents of the Royal Society of Medicine
The President of the Royal Society of Medicine is the head of the Royal Society of Medicine. Presidents were elected biennially by the Fellows of the Society up until 2014 when the charter changed. Presidents are now elected every three years.
The President oversees the running of the Society and chairs its council meetings. Almost all presidents have been nominated following many years' service to the Society.List of presidents of the Royal Society
The President of the Royal Society (PRS) is the elected Head of the Royal Society of London who presides over meetings of the society's council.
After informal meetings at Gresham College, the Royal Society was officially founded on 28 November 1660 when a group of academics decided to found "a Colledge for the Promoting of Physico-Mathematicall Experimentall Learning", acquiring a Royal Charter on 15 July 1662. The Royal Charter nominated William Brouncker as president, and stipulated that future presidents should be elected by the Council and Fellows of the society at anniversary meetings each year on St. Andrew's Day (30 November).
The details of the presidency were described by the second Royal Charter, which did not set any limit on how long a president could serve. There were considerable fluctuations in the president's term of office until well into the 19th century. By then, sentiment had turned against electing wealthy amateurs solely because they might become patrons of the society, and in 1847 the society decided that Fellows would be elected solely on scientific merit. Since the 1870s it has been usual (with a few exceptions) for each President to serve for exactly five years. Under the current statutes, a president cannot serve for more than five years. The current President is Venkatraman Ramakrishnan who began his 5-year tenure in 2015.Historically, the duties of the president have been both formal and social. Under the Cruelty to Animals Act 1876, the President was one of only a few people authorised to certify that a particular experiment on an animal was justified, and in addition he acted as the government's chief (albeit informal) advisor for scientific matters. At the same time, the President was tasked with entertaining distinguished foreign guests and scientists.The changeover of presidents occurs on the Royal Society Anniversary Day, the weekday on or nearest to 30 November, after the departing President's Anniversary Address.National Institute for Medical Research
The National Institute for Medical Research (commonly abbreviated to NIMR), was a medical research institute based in Mill Hill, on the outskirts of north London, England. It was funded by the Medical Research Council (MRC);
In 2016, the NIMR became part of the new Francis Crick Institute, which was constructed next to St Pancras railway station in the Camden area of central London.Otto Loewi
Otto Loewi (3 June 1873 – 25 December 1961) was a German-born pharmacologist and psychobiologist who discovered the role of acetylcholine as an endogenous neurotransmitter. For his discovery he was awarded the Nobel Prize in Physiology or Medicine in 1936, which he shared with Sir Henry Dale, who was a lifelong friend who helped to inspire the neurotransmitter experiment. Loewi met Dale in 1902 when spending some months in Ernest Starling's laboratory at University College, London.Terence Cawthorne
Sir Terence Edward Cawthorne FRCS (29 September 1902 – 22 January 1970) was a British surgeon specialising in otorhinolaryngology (ENT). He was knighted in 1964.Tollington School
Tollington School (1901-1967) was a selective, coeducational grammar school in Muswell Hill, London, England. For the present school on this site, see Fortismere School.Vagusstoff
Vagusstoff (literally translated from German as "Vagus Substance") refers to the substance released by stimulation of the vagus nerve which causes a reduction in the heart rate. Discovered in 1921 by physiologist Otto Loewi, vagusstoff was the first confirmation of chemical synaptic transmission and the first neurotransmitter ever discovered. It was later confirmed to be acetylcholine, which was first identified by Sir Henry Hallett Dale in 1914. Because of his pioneering experiments, in 1936 Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Dale.Vincent Warren Low
Vincent Warren Low (1867–1942) was a British surgeon.
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