John Hughes (neuroscientist)
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John Hughes (born 6 January 1942) is a British
neuroscientist A neuroscientist (or neurobiologist) is a scientist specializing in neuroscience that deals with the anatomy and function of neurons, Biological neural network, neural circuits, and glia, and their Behavior, behavioral, biological, and psycholo ...
who shared the 1978
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the Lasker Award, prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Phys ...
for the discovery of
met-enkephalin Met-enkephalin, also known as metenkefalin ( INN), sometimes referred to as opioid growth factor (OGF), is a naturally occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. It is one of the two forms of enkep ...
and
leu-enkephalin Leu-enkephalin is an endogenous opioid peptide neurotransmitter with the amino acid sequence Tyr-Gly-Gly-Phe-Leu that is found naturally in the brains of many animals, including humans. It is one of the two forms of enkephalin; the other is met ...
. This discovery demonstrated that
opiate An opiate is an alkaloid substance derived from opium (or poppy straw). It differs from the similar term ''opioid'' in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain ( ...
drugs exert their effects on the
human brain The human brain is the central organ (anatomy), organ of the nervous system, and with the spinal cord, comprises the central nervous system. It consists of the cerebrum, the brainstem and the cerebellum. The brain controls most of the activi ...
by mimicking endogenous
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...
s, the
opioid peptide Opioid peptides or opiate peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these p ...
s.


Education

Hughes was born and grew up in
South London South London is the southern part of Greater London, England, south of the River Thames. The region consists of the Districts of England, boroughs, in whole or in part, of London Borough of Bexley, Bexley, London Borough of Bromley, Bromley, Lon ...
. He received BSc and PhD degrees from
King's College London King's College London (informally King's or KCL) is a public university, public research university in London, England. King's was established by royal charter in 1829 under the patronage of George IV of the United Kingdom, King George IV ...
.


Career and research

After his PhD, Hughes did
postdoctoral research A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). Postdocs most commonly, but not always, have a temporary acade ...
at
Yale Medical School The Yale School of Medicine is the medical school of Yale University, a private research university in New Haven, Connecticut. It was founded in 1810 as the Medical Institution of Yale College and formally opened in 1813. It is the sixth-oldest m ...
, where he studied the effects of
angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...
on the
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
. He took a position as lecturer in Pharmacology at
Aberdeen University The University of Aberdeen (abbreviated ''Aberd.'' in post-nominals; ) is a public research university in Aberdeen, Scotland. It was founded in 1495 when William Elphinstone, Bishop of Aberdeen and Chancellor of Scotland, petitioned Pope Al ...
, where he had a laboratory in
Marischal College Marischal College ( ) is a large granite building on Broad Street in the centre of Aberdeen in north-east Scotland, and since 2011 has been the headquarters of Aberdeen City Council. The building was constructed for and is on long-term lease fr ...
, and also collaborated in research with
Hans Kosterlitz Hans Walter Kosterlitz FRS (27 April 1903 – 26 October 1996) was a German-born British biochemist. Biography Hans Walter Kosterlitz was born on 27 April 1903 in Berlin. He was the elder son of Bernhard Kosterlitz, a physician, and Selma ...
. He went on to become Reader in Pharmacological Biochemistry, and subsequently Professor, at
Imperial College London Imperial College London, also known as Imperial, is a Public university, public research university in London, England. Its history began with Prince Albert of Saxe-Coburg and Gotha, Prince Albert, husband of Queen Victoria, who envisioned a Al ...
. Later, he became Director of the Parke-Davis Neuroscience Centre at the
University of Cambridge The University of Cambridge is a Public university, public collegiate university, collegiate research university in Cambridge, England. Founded in 1209, the University of Cambridge is the List of oldest universities in continuous operation, wo ...
, where he is now an Emeritus Fellow of Wolfson College. He is also a
Fellow of the Royal Society Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the Fellows of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural science, natural knowledge, incl ...
.


Discovery of enkephalins

While working with Kosterlitz at Aberdeen, Hughes helped discover the
enkephalin An enkephalin is a pentapeptide involved in regulating nociception (pain sensation) in the body. The enkephalins are termed endogenous ligands, as they are internally derived (and therefore endogenous) and bind as ligands to the body's opioid ...
peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
s. Kosterlitz had developed
assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity ...
s for responses to opiate drugs, using pieces of
guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy ( ), is a species of rodent belonging to the genus ''Cavia'', family Caviidae. Animal fancy, Breeders tend to use the name "cavy" for the ani ...
intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
and
mouse A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...
vas deferens The vas deferens (: vasa deferentia), ductus deferens (: ductūs deferentes), or sperm duct is part of the male reproductive system of many vertebrates. In mammals, spermatozoa are produced in the seminiferous tubules and flow into the epididyma ...
. Hughes sought to determine whether molecules present in
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
s could mimic the effects of the drugs. Reflecting in 1995 about that time, Hughes said: "From my personal point of view, I think that the reason I got interested in searching for an endogenous opioid-like substance is that I had been previously involved during my PhD student work in looking at non-adrenergic, noncholinergic innervation of various blood vessels and that's what my PhD thesis was eventually written on." He would bicycle daily to a
slaughterhouse In livestock agriculture and the meat industry, a slaughterhouse, also called an abattoir (), is a facility where livestock animals are slaughtered to provide food. Slaughterhouses supply meat, which then becomes the responsibility of a mea ...
, where he would trade bottles of whiskey to the butchers in exchange for pig heads, and he subsequently prepared brain
extracts An extract (essence) is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures or absolutes or dried and powdered. The aromatic principles of man ...
using
acetone Acetone (2-propanone or dimethyl ketone) is an organic compound with the chemical formula, formula . It is the simplest and smallest ketone (). It is a colorless, highly Volatile organic compound, volatile, and flammable liquid with a charact ...
. After testing many samples in Kosterlitz's assays, the two scientists were able to isolate and identify two peptides, met- and leu-enkephalin, as naturally occurring molecules from the brain, that have activity resembling
opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
s. Hughes and Kosterlitz first announced their findings at a scientific conference in May 1974, and published the structures of the two enkephalins in 1975. In 1978, they shared the Lasker award with
Solomon H. Snyder Solomon Halbert Snyder (born December 26, 1938) is an American neuroscientist who has made wide-ranging contributions to neuropharmacology and neurochemistry. He studied at Georgetown University, and has conducted the majority of his research a ...
, and Hughes in particular was credited with predicting the existence of endogenous opioids.


References

{{DEFAULTSORT:Hughes, John 1942 births Living people English neuroscientists English pharmacologists Alumni of King's College London Scientists from London Academics of the University of Aberdeen Academics of Imperial College London Fellows of Wolfson College, Cambridge Fellows of the Royal Society Recipients of the Albert Lasker Award for Basic Medical Research