John Hughes (neuroscientist)
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John Hughes (born 6 January 1942) is a British
neuroscientist A neuroscientist (or neurobiologist) is a scientist who has specialised knowledge in neuroscience, a branch of biology that deals with the physiology, biochemistry, psychology, anatomy and molecular biology of neurons, neural circuits, and glial ...
who shared the 1978 Albert Lasker Award for Basic Medical Research 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 A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In ...
and leu-enkephalin. This discovery demonstrated that opiate drugs exert their effects on the
human brain The human brain is the central organ (anatomy), organ of the human nervous system, and with the spinal cord makes up the central nervous system. The brain consists of the cerebrum, the brainstem and the cerebellum. It controls most of the act ...
by mimicking endogenous neurotransmitters, the
opioid peptide Opioid 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 peptides vary, but t ...
s.


Education

Hughes was born and grew up in South London. He received BSc and PhD degrees from King's College London.


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). The ultimate goal of a postdoctoral research position is to pu ...
at
Yale Medical School The Yale School of Medicine is the graduate medical school at 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. The primary te ...
, 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 adren ...
on the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
. He took a position as lecturer in Pharmacology at
Aberdeen University , mottoeng = The fear of the Lord is the beginning of wisdom , established = , type = Public research universityAncient university , endowment = £58.4 million (2021) , budget ...
, 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 acted as the headquarters of Aberdeen City Council. However, the building was constructed for and is on long- ...
, 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 A reader is a person who reads. It may also refer to: Computing and technology * Adobe Reader (now Adobe Acrobat), a PDF reader * Bible Reader for Palm, a discontinued PDA application * A card reader, for extracting data from various forms of ...
in Pharmacological Biochemistry, and subsequently Professor, at
Imperial College London Imperial College London (legally Imperial College of Science, Technology and Medicine) is a public research university in London, United Kingdom. Its history began with Prince Albert, consort of Queen Victoria, who developed his vision for a cu ...
. Later, he became Director of the Parke-Davis Neuroscience Centre at the
University of Cambridge The University of Cambridge is a public collegiate research university in Cambridge, England. Founded in 1209 and granted a royal charter by Henry III in 1231, Cambridge is the world's third oldest surviving university and one of its most pr ...
, 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 judges of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural knowledge, including mathemat ...
.


Discovery of enkephalins

While working with Kosterlitz at Aberdeen, Hughes helped discover the
enkephalin An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephali ...
peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
s. Kosterlitz had developed assays 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'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
intestine and mouse
vas deferens The vas deferens or ductus deferens is part of the male reproductive system of many vertebrates. The ducts transport sperm from the epididymis to the ejaculatory ducts in anticipation of ejaculation. The vas deferens is a partially coiled tube ...
. Hughes sought to determine whether molecules present in
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
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, where he would trade bottles of whiskey to the butchers in exchange for pig heads, and he subsequently prepared brain
extracts An extract 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, absolutes or in powder form. The aromatic principles of many spices, nuts, ...
using
acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...
. 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 substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
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, 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