Last month a pioneering pharmacologist died. This post is one of the many tributes to his life .
Thank you William Grimes of the NYT for letting me know.
Dr. Alfred Goodman Gilman, was the son of the founding head of pharmacology at the Albert Einstein School of Medicine. The senior Gilman was also the original author of my graduate school bible, the thick and heavy, Goodman and Gilman’s: The Pharmacological Basis of Therapeutics. In fact, the Dr. Alfred Goodman Gilman was honored by being named after his father’s co-author. I guess it’s no surprise coming from this legacy that Dr. Gilman was so accomplished.
When I first entered graduate school, he had recently won the Nobel Prize. Very simply, Dr. Gilman discovered a class of proteins that utilized Guanosine-5'-triphosphate (GTP) to initiate signaling cascades within cells.
All cells, almost all secondary messages, involved in almost all cellular functions, in all species, from yeast to mammals utilize GTP as a second messenger in cells.
- Now, that’s Nobel Prize work.
This fundamental finding was central to my studies in graduate school. My first laboratory rotation was concerning the small Rho GTPase, Cdc42, in the induction of filopodia. Using computational drug design, my second rotation investigated the polymerization of microtubules, their GTP binding sites and their unwillingness to depolymerize when GTP binding was competitively inhibited with the anticancer drug, taxol.
Suffice to say in the 1990’s, GTP and its extracellular, transmembrane receptors, G-protein coupled receptors (GPCR), were the focus of many, many laboratories, academic and otherwise.
And that’s not ill-founded or ill-funded. GPCR-targeting drugs represent 30-40% of ALL marketed pharmaceuticals, falling into diverse mechanisms from antihistamines and opioids to adrenergic and dopaminergic categories. It can be said that today’s big pharma's R & D departments are built around the discovery of novel GPCRs, their natural ligands and the development of synthetic inhibitors. Even the F.D.A. has a fast track approval process for ‘orphan GPCRs’ those receptors without a known ligand.
So, every time you take Claritin, Zantac, or even OxyContin, go ahead and thank Dr. Gilman.
May his memory be eternal.