Acta Biologica Tomus XL. Fasciculi 1-4. [antikvár]

Acta Biol. Szeged. 40, pp. 5-9. (1994) cholinesterase - from basic science to clinical practice A speech on the occasion of the conferment of'Doctor Honoris Causa' József Attila University, Szeged 21 September 1993 A. D. Smith Department of Pharmacology, Oxford University South Parks Road, Oxford. 0X13QT, England Rektor, members of the Council of the University, Ladies and Gentlemen: It is with great pleasure and with a sense of honour that I stand before you today. I would like to tell you a little about the process of discovery in science as I have been fortunate to experience it. The topic I have chosen is: "Cholinesterase - from basic science to clinical practice". What I will try to show you is how experiments carried out to answer basic questions of science can lead, in time, to a contribution to the practice of medicine. The experiments on Cholinesterase that I shall describe were not carried out with any practical application in mind; at the time they were done I was not even aware of the problem in clinical medicine to which they were eventually to provide a solution. I would like to illustrate four of the many factors that contribute to the path of discovery: first, the primacy of experimental observation over current dogma; second, the dedication and determination of the young scientist; third, curiosity, without which life in science is barren; fourth, the chance encounter with a colleague. First, let me illustrate how experimental observation can challenge current dogma. I expect that everyone here will have heard of the chemical transmitter acetylcholine, which is secreted from certain nerves in the brain and in the peripheral nervous system. Its best known role is as the transmitter at the junction between the motor nerve and the muscle fibre: it is the agent that causes contraction of the muscles in your legs and arms. In order to stop the muscle from going into a spasm it is obviously necessary to get rid of the acetylcholine as soon as the muscle has contracted: that is the role of Cholinesterase, an enzyme which hydrolyses the acetylcholine to inactive products. Cholinesterase exists in the body in two different forms: the form that destroys acetylcholine after it has been released from nerves is called acetylcholinesterase and is present in the membranes of the muscle and nerve. The second form is called nonspecific Cholinesterase and is present free in the blood plasma. No one knows the function of the Cholinesterase in the blood, but it is known that it is in the blood because it is secreted from the liver. By the early 1970's it was established that the two forms of Cholinesterase were separate proteins and we now know that they are coded