William Anthony Devane

 
 

William Anthony Devane was raised in Chicago, IL, and moved to St. Louis, MO to attend Graduate school in the Department of Pharmacological and Physiological Sciences at Saint Louis University School of Medicine. He chose to work in Dr. Allyn Howlett’s laboratory at a very exciting time, as the Howlett laboratory had determined that a series of Pfizer Co. cannabinoid analogs – based upon the structure of 11-OH-Tetrahydrocannabinol (THC) – were able to signal via a Gi G-protein and inhibition of adenylyl cyclase mechanism, and therefore behaved as G-protein-coupled receptor agonists. Bill joined the laboratory just at the time that Pfizer provided the substrate for tritiation to [3H]CP55940 and the US National Institutes of Health (NIH) funded the project to develop the radioligand binding assay. Bill enthusiastically took the project forward as his Ph.D. dissertation work and eventually published the seminal paper (Devane et al., 1988) – and in doing so initiated work by myriad laboratories world-wide to characterize localization and function of cannabinoid receptors throughout the brain and body. During his Graduate school years, Bill expanded his interest into Hindu religious literature and thought, which, along with photography, bicycling and hiking, became his life-long activities.

Bill subsequently headed to Jerusalem, to work in Dr. Raphael Mechoulam's laboratory, where his project was to identify a possible endogenous ligand of the cannabinoid receptor. First, Bill developed a sensitive assay using a known potent cannabinoid agonist, [3H]HU-243 (Devane et al., 1992a) – to check compounds for binding to the receptor. Then Bill and Dr. Lumír Hanuš, a visiting scientist from Brno, undertook the massive effort to find a compound, in extracts of pig brains, that binds to the cannabinoid receptor. After a large number of chromatographic separations Bill and Dr. Hanuš isolated a minute amount of a compound which bound to the receptor. On March 24, 1992, the last isolation was complete, and Bill had dubbed it “anandamide” – “ananda,” the Sanskrit word for bliss.

Anandamide was sent to Professor Roger Pertwee, in Scotland, who showed that pharmacologically it behaved as THC, the plant cannabinoid agonist. High resolution mass spectral analysis by Professor Mandelbaum at the Technion in Haifa and NMR studies in Jerusalem finally led to the elucidation of the structure. Dr. Aviva Breuer synthesized anandamide. Thusly, the major goal of finding the first endogenous cannabinoid was achieved. Bill was a major contributor to this important project (Devane et al., 1992b) – a discovery that opened up vast development of research on the biochemistry and pharmacology of endogenous eicosanoid agonists for cannabinoid receptors.

After his Israeli postdoctoral research, Bill left the Mechoulam laboratory and started research in the USA with Dr. Julius Axlerod’s group at NIH. Bill collaborated with NIH researchers to demonstrate that anandamide could bind to the de-orphanized gene product identified to be the CB1 cannabinoid receptor (Felder et al., 1993), and to characterize the biological functions promoted by anandamide (Crawley et al., 1993; Collin et al., 1995; Mackie et al., 1993). This work led to identification of analogs of anandamide that exhibited binding to either CB1 or CB2 cannabinoid receptors (Priller et al., 1995). Bill’s work with Dr. Axelrod also led to our greater understanding of the function of the enzyme Fatty Acid Amide Hydrolase (Arreaza et al., 1997; Devane and Axelrod, 1994).

After a brief academic job at the University of Wisconsin College of Pharmacy, Bill relocated to Dr. Billy Martin’s Department at Medical College of Virginia, Virginia Commonwealth University, where he continued to explore endogenous ligands for cannabinoid receptors via a K01 award from NIH.  Unfortunately, Bill’s health began to falter, and became a considerable impediment to the progression of his scientific research career. Nevertheless, Bill continued to contribute to the cannabinoid field (Howlett et al., 2002). 

His Grandfather was Irish, which allowed Bill to obtain an Irish Passport and in 2006 he moved to Galway City on the West Coast of Ireland. Dr. David Finn, Professor of Pharmacology and Therapeutics at the National University of Ireland (NUI), Galway, tells the story of how Bill called him up out of the blue one day that year and asked to meet. Dr. Finn was amazed to learn that Bill was now living in Galway and had expressed a desire to return to science and work at the University. Bill initially got a job with Professor Lokesh Joshi at NUI Galway working in the area of glycoscience, and it wasn’t long before he started to do some collaborative work with Dr. Finn on cannabinoid pharmacology. Subsequently, with the support of NUI Galway, Bill secured a Career Re-Entry Fellowship from the Wellcome Trust in 2011 to work on the compound leelamine. Despite continuing difficulties with his health, Bill managed to generate some very interesting, novel data which were presented at international scientific conferences (Devane et al., 2012; Devane and Finn, 2013; Llorente-Berzal et al., 2017).  Bill was regarded in very high esteem at NUI Galway, his very sharp mind and seminal contributions to cannabinoid pharmacology were an inspiration to students and early career researchers.


Bill’s gentle, honest, conversational and inquisitive nature endeared him to many.  In 2014, he took early retirement from NUI Galway due to ill health, and continued to live in Galway where he enjoyed life and good friendships, and sang in the choir of The Franciscan Abbey in the city centre.   


We all have enjoyed our conversations with Bill over the many years at ICRS and European Cannabinoid meetings. All will miss these invigorating conversations and interchanges with Dr. Devane. Our heartfelt condolences to Bill’s family at this time.


Rest in peace, Bill. We miss you.


The International Cannabinoid Research Society



Contributed by Allyn Howlett, Raphael Mechoulam, Lumír Hanuš, Jason Schechter and David Finn



Reference List

Arreaza G, Devane W A, Omeir R L, Sajnani G, Kunz J, Cravatt B F and Deutsch D G (1997) The Cloned Rat Hydrolytic Enzyme Responsible for the Breakdown of Anandamide Also Catalyzes Its Formation Via the Condensation of Arachidonic Acid and Ethanolamine. Neurosci Lett 234:59-62.

Collin C, Devane W A, Dahl D, Lee C J, Axelrod J and Alkon D L (1995) Long-Term Synaptic Transformation of Hippocampal CA1 Gamma-Aminobutyric Acid Synapses and the Effect of Anandamide. Proc Natl Acad Sci U S A 92:10167-10171.

Crawley JN, Corwin R L, Robinson J K, Felder C C, Devane W A and Axelrod J (1993) Anandamide, an Endogenous Ligand of the Cannabinoid Receptor, Induces Hypomotility and Hypothermia in Vivo in Rodents. Pharmacol Biochem Behav 46:967-972.

Devane WA and Axelrod J (1994) Enzymatic Synthesis of Anandamide, an Endogenous Ligand for the Cannabinoid Receptor, by Brain Membranes. Proc Natl Acad Sci U S A 91:6698-6701.

Devane WA, Breuer A, Sheskin T, Jarbe T U, Eisen M S and Mechoulam R (1992a) A Novel Probe for the Cannabinoid Receptor. J Med Chem 35:2065-2069.

Devane WA, Dysarz F A, III, Johnson M R, Melvin L S and Howlett A C (1988) Determination and Characterization of a Cannabinoid Receptor in Rat Brain. Mol Pharmacol 34:605-613.

Devane WA, Hanus L, Breuer A, Pertwee R G, Stevenson L A, Griffin G, Gibson D, Mandelbaum A, Etinger A and Mechoulam R (1992b) Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor. Science 258:1946-1949.

Devane WA, Stevens D, Finn DP, Nebane N, Song ZH, Peters D, Crawford D, Walker JM, Applegate B, Kennish J, Cassidy MP, Selley D, and Dewey WL (2012).  Leelamine, a novel diterpene, exhibits cannabimmetic effects in CB1 receptor knockout mice. 22nd Annual Symposium on the Cannabinoids, International Cannabinoid Research Society, P2-10.

Devane WA and Finn DP (2013).  Pharmacological Characterisation Of A Binding Site For Leelamine.  The 6th European Workshop on Cannabinoid Research, Dublin, April 2013.  P015.

Felder CC, Briley E M, Axelrod J, Simpson J T, Mackie K and Devane W A (1993) Anandamide, an Endogenous Cannabimimetic Eicosanoid, Binds to the Cloned Human Cannabinoid Receptor and Stimulates Receptor-Mediated Signal Transduction. Proc Natl Acad Sci U S A 90:7656-7660.

Howlett AC, Barth F, Bonner T I, Cabral G, Casellas P, Devane W A, Felder C C, Herkenham M, Mackie K, Martin B R, Mechoulam R and Pertwee R G (2002) International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors. Pharmacol Rev 54:161-202.

Llorente-Berzal A, Harhen B, Devane WA, Finn DP (2017). Leelamine, a low affinity CB1 receptor ligand, has cannabinoid-like behavioural effects in rats. 8th European Workshop on Cannabinoid Research. London, United Kingdom. September 2017. Poster presentation.

Mackie K, Devane W A and Hille B (1993) Anandamide, an Endogenous Cannabinoid, Inhibits Calcium Currents As a Partial Agonist in N18 Neuroblastoma Cells. Mol Pharmacol 44:498-503.

Priller J, Briley E M, Mansouri J, Devane W A, Mackie K and Felder C C (1995) Mead Ethanolamide, a Novel Eicosanoid, Is an Agonist for the Central (CB1) and Peripheral (CB2) Cannabinoid Receptors. Mol Pharmacol 48:288-292.


An interview with Dr. Devane:   http://youtu.be/X-9FP-xes1E


1992 New York Times article featuring Dr. Devane’s discoveries.


Dr. Devane in Zach Klein’s documentary,  The Scientist, filmed at ICRS2012.







































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On Oct 15, 2018, at 12:28 PM, Dale Deutsch <dale.deutsch@stonybrook.edu> wrote:

 

Hi All--
Thank you for this wonderful description of Bill's life and work.  He was also very kind and interactive with me and I was glad to have publish a paper with him that is referenced in the biography.  The paper helped clarify the fact that FAAH can catalyze the condensation of arachidonic acid and ethanolamine to produce anandamide (the reverse reaction) and cleared up an early experiment of ours. 

 "At first we mistakenly reported an enzymatic activity independent of the fatty acid amide hydrolase (FAAH) and calcium for the synthesis of AEA (Deutsch and Chin, 1993), but then followed up with collaborators to help elucidate the correct pathways. This misstep was explained by the condensation of ethanolamine with phenylmetylsulfony fluoride, whose product ran the same as AEA on thin layer chromatography”

(Bill Devane, personal communication circa 1994)

 Another memories that sticks out for me was my visit to him at the University of Wisconsin Chemistry Department where he was happy and searching for other endogenous ligands other than anandamide and also my visit to him at the University of Virginia where he was experiencing bouts of depression.      --Best Regards, Dale

Dale Deutsch
Department of Biochemistry and Cell Biology
Stony Brook University
Stony Brook, NY 11794












 

It is with great sadness that ICRS writes to inform you –

Will (Bill) Devane passed away late in the night, October 11th, 2018.

Roger Pertwee and Bill Devane // ICRS2012
Lumír Hanuš and Bill Devane // Dublin 2009