Activation of prothrombin.

Species differences of clotting factors in ox, dog, horse, and man: proaccelerin and accelerin.

children, owing to their upsetting experiences,are liable to become the troublesomepeople of tomorrow, and the community owes it to itself and to them to see that they get the best considerationpossible, from the moment the suit is instituted. I am awarethat any effective measures for better securing the welfare of these children might involve heavy public expense. However, as the public spendsfreely upon horsesand greyhoundsand the excitements which those animals provide, I regard with contemptany objection basedon expense. There is anothermatter to which I would like to refer. Every year there is an increasing tendency in the professionsto specializemore and more at the expenseof general knowledge. It is no longer considerednecessary, or even desirable, for a professional man to have broadened his general outlook or to have fortified his mind to withstand the narrowing tendency of having oBly one intellectual interest, by building the professional superstructure upon a sound and lastmg general education. I may be expressingan outmodedidea when I tell you that it is my clear conviction that an advancedbasiceducation, either in the classics or in modern languagesand comparativephilology, or in mathematics,or in history, or in psychology, makes the brain a better machine,and the mind more receptive over a wide field, and the judgementbetter balancedthan they are without the aid of an early 'comprehensivetraining. Let me take two instances to illustrate what I am stressing. One of the greatestand most Ilberal-minded Australian lawyers of all time was Leverrier. His legal knowledge was immense, his judgement perfectly balanced. But he was, as many of you may remember,not only a lawyer, but also a scientistof great attainments,a mathematician and a man possessedof wide general learning. All these contributed to his greatnessas a lawyer. Another great Australian, whom many of you will remember, was Edgeworth David. As a geologist he combined a great knowledge of detail of Australian geology with a remarkable capacity for evolving from detail a clear and comprehensivepicture of the geological structure and history of the continent as a whole. Edgeworth David before he became a geologist was a classical scholar of considerablelearning. Each one of you, no doubt, will readily call to mind from your own experienceprofessional men graced with the imprint of general learning; men who can leave the highroad of some specialized pursuit, and enjoy, with delight to themselvesand their friends, the broad and lovely fields and bushlandsof knowledge. I suggest,therefore,that the greatquestionof education, as it affects our two professions,is one which a society such as this might well examine. Let it be understood,however, that I am not attacking specialization; it is both desirableand inevitable. What I am suggestingis that there should be a proper foundation beneathit. At the risk of detaining you a little longer than I should, I pass to the last matter to which I invite your attention. We of the British race have developedover the centuries a form of constitutional government which particularly suits our character, our love of freedom and our deep dislike of anything savouring of autocracy. And we have developedconceptsof law, and of the rule of Jaw, which are admirably designed to secure us from invasion of our liberties, and to protect us from the dictatorship either of an individual or of any group of individuals claiming to exercise executive authority without responsibility either to the law or to the people. As a result of the last two world wars, those precious things which we have inherited, which are the envy of less fortunate peoples,are in grave danger of being lost. That danger exists because the people, having enjoyed liberty for so long, do not notice its existence,and tend to neglect their duty of understandingand preserving it for themselvesand for their children. The continuance of parliamentary government as we have known it, of the responsibilityof parliamentand the executive governmentto the people, and of the rule of law, dependsentirely upon a strong and articulate desire for their continuanceon the part of a substantialsection of the community. You may ask what this has to do with a medico-legal society. Just this: without leadershipno community can be anything but a decadent rabble. I use the word \"leadership\" in a large sense,as comprising not merely the active leaders of a State, but also the many who have a guiding or enlightening influence upon others. So far democracy has succeededin our land, because leadership, loyal to its principles, has not been lacking. This has happenedbecausea substantial portion of the people-andnote that I say \"portion' and not \"class\"has qualified itself for leadershipeither by a broad and liberal education gained scholastically, or by balanced wisdom acquired by wide experienceor wide reading. That is where we enter the picture. There is no longer any leisured class to provide part of the necessary leadership; because,say what you like about the leisured groups of the past, they provided many men who devoted their lives to the service of the community. More and more, the generalmassof the people will come to respect a man for his learning, be it learning in science, art, music, literature, or in one of the professions, or in anything else. These are the men upon whom depends the survival of democracy,of civil liberty, of the rule of law, of the responsibility of those who govern to those who are governed. Therefore do I stress the first and paramount duty of all professional men-particularly of the lawyers because of their understanding of constitutional principles-to hold their education and their knowledge of humanity in trust for the benefit of the people, just as much as they hold their professional skill in trust for thosewho seekit. In conclusion, I hope that such thoughtsas I have been tempted to utter in the course of this address, if not acceptable to Minerva, might possibly be provocative enough to stimulate useful ideas in others. As I said, humanity is only just beginning to understanditself and to study itself scientifically. This society has sprung into life at one of the greatest and most anxious periods of all history; at a time when it was never more necessary for all men of special learning to accept their responsibilities towards the community. Let us, therefore, following the example of other learned associationsin our land, proceed to fulflll our aims and ambitions of useful achievement.

The physiological activation of prothrombin.

CEIUTAIN paradoxical cflkts of liusscll’s viper vciioni (KVV) oil blood coagulation have been recognized for some tinic. An intravenous injection of a large dose into a n animal is ininicdiately fatal, and autopsy rcvcals widcspread intravascular clotting (Lamb and Harina, 1903). Iiijcction of snialler, sublethal doses is fidlowed by a period of reduced blood coagulability arid fibrinogcnopenia (Arthus, 1920). Irr vitro, the coi~vcrsc cffcct has been Iiotcd, concciitrated solutions being shown to have anticoagulant activity, and iiiorc dilute solutioiis to xcclcratc coagulation (Brazil and Vcllard, 1928). The inhibitory cffcct of IIVV in high concentration (2-25 per cent) has recently been studied in great detail by Weiickcrt and Nilssori (1955). They concluded that tlic anticoagulant action is not due to a property inherent in the vcnoni but to tlic release from prothronibin of a heparin-like anticoagulant. We believe this to bc aii incorrect interpretation, as w e I-lave obtained from KVV by paper electrophoresis a principle which appears to bc purely anticoagulant. Wllilc this investigation was in progress wc discovcrcd tha t Grasset and Schwartz (1955) had previously found RVV to contain an anticoagulant substance. The following results arc prescntcd as a coiifirniation and extension of their work.

The separation and properties of an anticoagulant principle from Russell's viper venom.

The role of anticoagulant therapy in surgery.

The experimental work supporting the view that thrombin is the activator of prothrombin was described in papers from our laboratory ten years ago.” Why, then, does this idea seem so surprising today? I think there are several reasons. First, most but not all of our demonstrations were concerned with prothrombin activation in 25 per cent sodium citrate solutions, and some of my readers may be inclined to feel that the “unphysiological conditions” make these experiments of consequence only in another domain. Second, much attention was attracted to the development of oral anticoagulants and, since mind is so constituted that, attention is fixed on one phenomenon a t a time, prothrombin activation was neglected. This was a peculiar neglect that, in most instances, consisted of a “brief review of the blood-clotting mechanism.” This mechanism was admittedly not understood, but a plausible notion is helpful even if iL obscures an accurate one. Third, clotting factors were disc.overed in many laboratories, including our own. Preoccupation with these developments became common. I once remarked that students of hemorrhagic diseases have “factorphilia” and will noteasily find a cure. Some of these factors are previously unrecognized properties of prothrombin, others are not, and some factors are being deleted, the evidence for them being inarlequate. For each one the claim has been made that it is essential for the activation of prothrombin. How many essential events are there in the conversion of prothrombin to thrombin? 1 do not know; perhaps no more than one, but I report my view that no factor besides thrombin is needed to do this work. In other words, I deny that these several factors are essential, and I see them function in support of the work thrombin does. In this way I can be comfortable with factorphilia, for there may be all kinds of circumstances and combinations of factors that support or retard the activation of prothrombin. This introduces the unifying point of view that all procoagulants and anticoagulants) be they ever so numerous, support or inhibit the activation of prothrombin by thrombin. Thus, simplification is one of the consequences of this way of considering our presenting facts. The first experiment to which I call attention was performed in 1948.’ 1 ly associates a.nd I had obtained excellent preparations of purified bovine prothrombin and also thrornbiii of high quality. About. 13,000 units of pro-

Activation of prothrombin.

Citations

Species differences of clotting factors in ox, dog, horse, and man: proaccelerin and accelerin.

The physiological activation of prothrombin.

The separation and properties of an anticoagulant principle from Russell's viper venom.

The role of anticoagulant therapy in surgery.

Is thrombin the only enzyme involved with prothrombin activation

Related Papers (5)

The activation of prothrombin.

Stability of prothrombin.

Studies on the activation of a serum “prothrombin-converting factor”

Prothrombin in Disorders of Blood

The Measurement of Prothrombin in Plasma: A Case of Prothrombin Deficiency