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LIVER IN REGULATION OF FIBRINOLYTIC ACTIVITY
1046
hypertrophy
incidence
tions thus
giddiness
and related syndromes. Further investigabe warranted. H.-R. WIEDEMANN M. TOLKSDORF Universitats-Kinderklinik, H.-G. HANSEN. Kiel, Germany. seem to
COLONIC LOSS OF POTASSIUM
SiR,-This is article (Feb. 8) moid Neoplasia.
a
Dr. Little’s Potassium Imbalance and Rectosig-
suggestion engendered by
on
Potassium secretion by the colon appears to lead to serious depletion in certain situations; possibly a contributing factor is tumour at or near the secretory site. I found some years ago that colonic epithelium (rat) contains high concentration (about that of renal cortex) of carbonic anhydrase. This fits with the electrolyte composition of the secretion,’ which is high in HCO3 and K+. It would be of interest to see whether acetazolamide would decrease K+ loss in the type of case described by Little. I am unaware of any physiological experiments on the effect of carbonic-anhydrase inhibition on colonic K+ secretion. Parsons2 showed that acetazolamide decreased HCO;; secretion from rat colon. Department of Pharmacology and Therapeutics, University of Florida College of Medicine, THOMAS H. MAREN. Gainesville, Fla., U.S.A.
BIOCHEMICAL UNITS
SIR,-Now that it is becoming usual, even in clinical circles, to describe the concentrations of electrolytes in milli-equivalents per litre, is it not time to use corresponding terms for non-electrolytes whose molecular weights are known ? Biological properties and chemical reactions alike depend on molar concentrations-on number, not mass, of the components. If concentrations were expressed in molar terms, their relative significance would be easier to appreciate. For example, glucose and urea have about the same concentration (4-5 milli-moles per litre) in the blood of normal fasting subjects, which is not obvious from the usual values in milligrammes per 100 ml. Perhaps moles should be used for electrolytes too. Equivalent and molar concentrations are identical for univalent electrolytes, so the use of both terms would not add confusion. Moles are probably even more apt than equivalents for such electrolytes as calcium and magnesium (which may exist to an unknown extent in un-ionised forms) and phosphate (the effective valency of which is
commonly undefined). Department of Physiology, Institute of Basic Medical Sciences, Royal College of Surgeons, London, W.C.2.
G. C. R. MORRIS.
METHYSERGIDE IN THE PROPHYLAXIS OF MIGRAINE own SIR,-My experience in the use of this drug in of the prophylaxis migraine is similar to that of Dr. Southwell and his colleagues (March 7), though the number of patients treated is smaller. It has been given to 17 patients who had an average of one attack a week for 2 years or longer, and who had not improved with dihydroergotamine, barbiturates, tranquillisers, or carbachol. 12 patients were female and 5 male. In 11 patients (9 female, 2 male) the frequency of attacks was reduced by 50% or more within a month, and within six months the 1. 2.
Thaysen, J. M. in Handbuch der experimentellen Pharmakologie (edited by M. M. Ussing); vol. 13, p. 485. Berlin, 1960. Parsons, D. S. Quart. J. exp. Physiol. 1956, 41, 410.
was
reduced
to one
in three months
or
less. Severe
experienced by 2 of the patients who did not improve, but were not complained of by any of the patients who improved, although on direct questioning 3 of these admitted to feeling giddy and off their food for a week or so but said that this was better than living in constant dread of a severe headache. A possible explanation for this lack of side-effects may be that the drug was given in doses of 3 mg. daily to start with, and the dose was gradually increased if symptoms did not improve. The E.E.G. in all the patients showed the characteristic response to photic stimulation which occurs in over 90% of migraine sufferers 1; and in 14 (10 female, 4 male) there was an abnormal amount of theta activity, which may be related to the severity of the headache.2 The 3 patients without excess
and
nausea were
theta activity
Burden
were
among
Neurological Institute, Bristol.
those who improved.
V. O. G. SMYTH.
LIVER IN REGULATION OF FIBRINOLYTIC ACTIVITY
great general interest in fibrinolytic enzymes, the role of the liver has been neglected. Yet there is much evidence that this organ plays an important role in regulating the normal fibrinolytic activity of human blood. This function of the liver seems to be primarily inhibitory. The evidence for this statement, to which we have to add some new observations of our own, is as follows: (a) in the first decade of this century, Nolf showed that in the dog a pronounced fibrinolytic reaction could be induced by injection of peptone after hepatectomy 3 ; (b) furthermore, it has been repeatedly demonstrated that with liver damage (for example through liver surgery, in carcinoma of the liver, and in hepatitis) fibrinolytic activity is increased 3; (c) Astrup has shown that the normal liver is the only human organ which does not exhibit any activator activity and that such activator activity can be found in cirrhotic livers; (d) finally, a fibrinolytic reaction is easier to induce with oral nicotinic acid in patients with cirrhosis of the liver or portacaval
SIR,-Despite
shunts.3 We have investigated what happens to fibrinolytic activity of the blood in patients temporarily deprived of all liver function. These observations were made during homotransplantation of the liver.4
Homotransplantation of the liver involves two essential steps in the recipient. The first step consists in freeing the liver from all adjacent tissue and dissecting and skeletonising those structures to be subsequently anastomosed to the homograft. This procedure brings about moderate increase in the fibrinolytic activity; but as soon as the first step is terminated, the fibrinolytic activity returns to normal. At the conclusion of this stage, the liver is attached only to the three constituents of the portal triad, the inferior vena cava, and the suprahepatic inferior vena cava. When, after an interval of hours, the actual transplantation is performed, the liver vessels have to be clamped off as the first step. From this moment until the new liver is in place the patient is functionally, and for a time anatomically, without a liver. The clamping off of the vessels is followed within minutes by a rapid and very pronounced increase of the fibrinolytic activity as measured by the euglobulin-lysis time and by the thrombelastograph. This is best interpreted as an absence of an inhibitory function of the liver leading to uninhibited plasminogen-activator activity. The activity disappears within one to several hours after the new liver has started to excrete bile. Golla, F. L., Winter, A. L. Electroenceph. clin. Neurophysiol. 1959. 11, 539. 2. Smyth, V. O. G., Winter, A. L. ibid. 1964, 16, 194. 3. For literature see K. N. von Kaulla, Chemistry of Thrombolysis. Human Fibrinolytic Enzymes. Springfield, Ill., 1963. 4. Starzl, T. W., Marchioro, T. L., von Kaulla, K. N., Hermann, G, Brittain, R. S., Waddell, W. R. Surg. Gynec. Obstet. 1963, 117, 657. 1.
1047 reasonable to ascribe the pronounced increase of in the liverless patient to circulating free activator, because the euglobulin-lysis time, which primarily measures this constituent of the fibrinolytic enzyme system, is reduced to a few minutes. The concomitant acceleration of plasma-clot lysis is abolished in vivo by the antiactivator e-aminocaproic acid. The inhibiting action of the liver is exercised by inactivation and/or metabolism of the circulating activator or else by release into the blood of antiactivator activity from the liver. This suggests that liver function and thromboembolic diseases might be related (which is not a new concept). Reduction of the circulating activator or strong antiactivator activity, both reflecting an exaggerated inhibitory activity of the liver, lead to reduced spontaneous fibrinolytic activity. Increased antiactivator activity has been found in patients with extended intravascular clotting.3 These observations suggest that the human fibrinolytic system exists permanently in a potentially activated state, It
seems
fibrinolytic activity
and that most of the circulating activator responsible for this potential activation is inhibited through an unknown mechanism by a normally functioning liver. Pathologically increased release of activator into the circulation, known to occur in a variety of circumstances,3 apparently cannot be sufficiently inhibited by the liver and a fibrinolytic reaction results. On this assumption, one might expect that the discovery of the compound which specifically interferes with the inhibitory action of the liver on fibrinolytic activity (much as prothrombin-depressing agents interfere with the synthesis of the prothrombin complex) would open new approaches to the treatment and prevention of thromboembolic diseases. The studies were supported by U.S.P.H.S. grant HE 05538-3 from the National Heart Institute. Department of Medicine,
University of Colorado School of Medicine, Denver, Colorado, U.S.A.
KURT N.
VON
KAULLA.
AN AUTOGENOUS ANTIBIOTIC?
SIR,-It is difficult to believe that the presence of lacticacid-producing microorganisms in mouth and throat, rectum, and vagina is mere coincidence. They have one property in common: they are antagonistic to proteolytic organisms (including certain pathogens) and also to putrefaction. This property has been attributed to the lactic acid produced by these organisms. They produce not only lactic acid, but also hydrogen peroxide.5-’ I experimented with a solution of 3-aminophthal hydrazide described by Langenbeck and Ruge,8 with the modification that I replaced the sodium carbonate used by these workers with an equivalent amount of sodium hydroxide. The results (unpublished) supported the view that the reaction between lactic acid and hydrogen peroxide is an autocatalytic chain reaction. In two previous communications 9 10pointed out that the antimicrobial property of human saliva could be explained by the interaction between the two metabolic products of these organisms-lactic acid and hydrogen peroxide. I was further able to show that hsemin oxidises lactic acid, and that in this reaction peroxide is formed. This could be significant in view of the observation that free lactic acid accumulates in inflamed tissues where free heme compounds are present as breakdown products of leucocytes and erythrocytes." There are probably many other oxidising systems in human tissues capable of inducing secondary oxidation of lactic acid with consequent autocatalytic formation of peroxide. The 5. McLeod, J. W., Gordon, J. Biochem. J. 1922, 16, 499. 6. Bertho, A., Gluck, H. Naturwissenschaft, 1931, 19, 88. as
7. 8. 9.
Fromageot, C., Roux, J. Biochem. Z. 1934, 267, 202. Langenbeck, W., Ruge, V. Ber. dtsch. chem. Ges. 1937, 70, 367. Kraus, A. Lancet, 1962, ii, 664. 10. Kraus, A. ibid. p. 1328. 11. Dubos, R. Biochemical Determinants of Microbial Diseases. Cambridge, Mass., 1954.
chain reaction may also play a part in the hitherto unexplained anti-infective action of ascorbic acid in the body. In the oxidation of ascorbic acid, hydrogen peroxide is formed,11-14 which in the presence of lactic acid could oxidise lactic acid. Jorissen and Belinfante 15 found that ascorbic acid can induce oxidation of lactic acid. Catalase, which may either be present in the tissue
or
be
produced by
the
proteolytic microorganisms
con-
cerned, could by breaking down hydrogen peroxide supply the molecular oxygen necessary to maintain continuous of the lactic-acid/peroxide system.
production
Antibiotics have been defined as " naturally produced inhibitors of the growth of organisms ". If this definition is accepted, the lactic-acid/peroxide system could truly be called an antibiotic produced by lactic streptococci and by lactobacilli. What other function the lactic-acid/peroxide system has in the human body or tissues is not clear. A. KRAUS. Twickenham, Middlesex.
Parliament Legislation
and Addiction
April 30, introducing the second reading of the Drugs (Prevention of Misuse) Bill,16 Mr. HENRY BROOKE, the Home Secretary, said that when an evil was manifestly growing he believed in acting to stop it. Though it had been suggested that legislation was premature, he considered that new powers were needed to deal with the social damage which was being caused by the increasing misuse of drugs, especially the amphetamines. The main purpose of the Bill was to make it an offence to be in unauthorised possession of these drugs and to prohibit their import without a licence. The prescription and sale of these drugs was already controlled by the Pharmacy and Poisons Act, 1933. But when drugs were being traded illicitly, often the only offence it was possible to prove was unauthorised possession, and the police needed additional powers to deal with traffickers in the drugs. Mr. Brooke had been out at night with the police to see for himself the social problems which faced them in Central London, and his visits had convinced him of the need for legislation. He said: " Amid all that sleazy stuff, the thing which impressed itself far the most deeply on my mind was the danger to the teenagers, both boys and girls, if this easy getting and taking of ’purple hearts ’ and pep pills went on growing and spreading." Our weapons for checking it were at present not effective, even with all the help that doctors and pharmacists could give. He asked the House for the new and stronger weapons in the Bill, to save youths and girls from a habit which could become a vice. Mr. ERNEST FLETCHER agreed that some further measures were necessary to deal with the misuse of these drugs. But we should realise that we were taking a novel, if justified, step. The State had always recognised that it had a duty to protect the public in certain circumstances from doing some things which might be harmful to them. That, however, was obviously a principle which one could not carry too far, because if that principle were accepted, one could extend it to the excessive consumption of alcohol, or of tobacco, or of a variety of other matters. We must also not delude ourselves that by passing the Bill we were dealing with the medical and social problems which lay behind the increase in addiction to these drugs. Lord BALNIEL supported the Bill, but also felt that any legislation which created a new criminal offence should be approached with caution. He was concerned that some young people apparently found the real world " so unrewarding and so unsatisfying and unconstructive and unexciting " that they turned to the unreal world of drugs. The Bill was repressive legislation, and repressive legislation almost never ON
12.
13. 14. 15. 16.
Barron, E. S. G., De Meio, R. H., Klemperer, F. J. biol. Chem. 1936, 112, 625. Holtz. P., Triem, G. Z. physiol. Chem. 1937, 248, 1. Schales, O. Ber. Dtsch. chem. Ges. 1938, 81, 447. Jorissen, W. P., Belinfante, F. Chem. Weekblad. 1933, 30, 618. See Lancet, April 11, 1964, p. 835.
hypertrophy
incidence
tions thus
giddiness
and related syndromes. Further investigabe warranted. H.-R. WIEDEMANN M. TOLKSDORF Universitats-Kinderklinik, H.-G. HANSEN. Kiel, Germany. seem to
COLONIC LOSS OF POTASSIUM
SiR,-This is article (Feb. 8) moid Neoplasia.
a
Dr. Little’s Potassium Imbalance and Rectosig-
suggestion engendered by
on
Potassium secretion by the colon appears to lead to serious depletion in certain situations; possibly a contributing factor is tumour at or near the secretory site. I found some years ago that colonic epithelium (rat) contains high concentration (about that of renal cortex) of carbonic anhydrase. This fits with the electrolyte composition of the secretion,’ which is high in HCO3 and K+. It would be of interest to see whether acetazolamide would decrease K+ loss in the type of case described by Little. I am unaware of any physiological experiments on the effect of carbonic-anhydrase inhibition on colonic K+ secretion. Parsons2 showed that acetazolamide decreased HCO;; secretion from rat colon. Department of Pharmacology and Therapeutics, University of Florida College of Medicine, THOMAS H. MAREN. Gainesville, Fla., U.S.A.
BIOCHEMICAL UNITS
SIR,-Now that it is becoming usual, even in clinical circles, to describe the concentrations of electrolytes in milli-equivalents per litre, is it not time to use corresponding terms for non-electrolytes whose molecular weights are known ? Biological properties and chemical reactions alike depend on molar concentrations-on number, not mass, of the components. If concentrations were expressed in molar terms, their relative significance would be easier to appreciate. For example, glucose and urea have about the same concentration (4-5 milli-moles per litre) in the blood of normal fasting subjects, which is not obvious from the usual values in milligrammes per 100 ml. Perhaps moles should be used for electrolytes too. Equivalent and molar concentrations are identical for univalent electrolytes, so the use of both terms would not add confusion. Moles are probably even more apt than equivalents for such electrolytes as calcium and magnesium (which may exist to an unknown extent in un-ionised forms) and phosphate (the effective valency of which is
commonly undefined). Department of Physiology, Institute of Basic Medical Sciences, Royal College of Surgeons, London, W.C.2.
G. C. R. MORRIS.
METHYSERGIDE IN THE PROPHYLAXIS OF MIGRAINE own SIR,-My experience in the use of this drug in of the prophylaxis migraine is similar to that of Dr. Southwell and his colleagues (March 7), though the number of patients treated is smaller. It has been given to 17 patients who had an average of one attack a week for 2 years or longer, and who had not improved with dihydroergotamine, barbiturates, tranquillisers, or carbachol. 12 patients were female and 5 male. In 11 patients (9 female, 2 male) the frequency of attacks was reduced by 50% or more within a month, and within six months the 1. 2.
Thaysen, J. M. in Handbuch der experimentellen Pharmakologie (edited by M. M. Ussing); vol. 13, p. 485. Berlin, 1960. Parsons, D. S. Quart. J. exp. Physiol. 1956, 41, 410.
was
reduced
to one
in three months
or
less. Severe
experienced by 2 of the patients who did not improve, but were not complained of by any of the patients who improved, although on direct questioning 3 of these admitted to feeling giddy and off their food for a week or so but said that this was better than living in constant dread of a severe headache. A possible explanation for this lack of side-effects may be that the drug was given in doses of 3 mg. daily to start with, and the dose was gradually increased if symptoms did not improve. The E.E.G. in all the patients showed the characteristic response to photic stimulation which occurs in over 90% of migraine sufferers 1; and in 14 (10 female, 4 male) there was an abnormal amount of theta activity, which may be related to the severity of the headache.2 The 3 patients without excess
and
nausea were
theta activity
Burden
were
among
Neurological Institute, Bristol.
those who improved.
V. O. G. SMYTH.
LIVER IN REGULATION OF FIBRINOLYTIC ACTIVITY
great general interest in fibrinolytic enzymes, the role of the liver has been neglected. Yet there is much evidence that this organ plays an important role in regulating the normal fibrinolytic activity of human blood. This function of the liver seems to be primarily inhibitory. The evidence for this statement, to which we have to add some new observations of our own, is as follows: (a) in the first decade of this century, Nolf showed that in the dog a pronounced fibrinolytic reaction could be induced by injection of peptone after hepatectomy 3 ; (b) furthermore, it has been repeatedly demonstrated that with liver damage (for example through liver surgery, in carcinoma of the liver, and in hepatitis) fibrinolytic activity is increased 3; (c) Astrup has shown that the normal liver is the only human organ which does not exhibit any activator activity and that such activator activity can be found in cirrhotic livers; (d) finally, a fibrinolytic reaction is easier to induce with oral nicotinic acid in patients with cirrhosis of the liver or portacaval
SIR,-Despite
shunts.3 We have investigated what happens to fibrinolytic activity of the blood in patients temporarily deprived of all liver function. These observations were made during homotransplantation of the liver.4
Homotransplantation of the liver involves two essential steps in the recipient. The first step consists in freeing the liver from all adjacent tissue and dissecting and skeletonising those structures to be subsequently anastomosed to the homograft. This procedure brings about moderate increase in the fibrinolytic activity; but as soon as the first step is terminated, the fibrinolytic activity returns to normal. At the conclusion of this stage, the liver is attached only to the three constituents of the portal triad, the inferior vena cava, and the suprahepatic inferior vena cava. When, after an interval of hours, the actual transplantation is performed, the liver vessels have to be clamped off as the first step. From this moment until the new liver is in place the patient is functionally, and for a time anatomically, without a liver. The clamping off of the vessels is followed within minutes by a rapid and very pronounced increase of the fibrinolytic activity as measured by the euglobulin-lysis time and by the thrombelastograph. This is best interpreted as an absence of an inhibitory function of the liver leading to uninhibited plasminogen-activator activity. The activity disappears within one to several hours after the new liver has started to excrete bile. Golla, F. L., Winter, A. L. Electroenceph. clin. Neurophysiol. 1959. 11, 539. 2. Smyth, V. O. G., Winter, A. L. ibid. 1964, 16, 194. 3. For literature see K. N. von Kaulla, Chemistry of Thrombolysis. Human Fibrinolytic Enzymes. Springfield, Ill., 1963. 4. Starzl, T. W., Marchioro, T. L., von Kaulla, K. N., Hermann, G, Brittain, R. S., Waddell, W. R. Surg. Gynec. Obstet. 1963, 117, 657. 1.
1047 reasonable to ascribe the pronounced increase of in the liverless patient to circulating free activator, because the euglobulin-lysis time, which primarily measures this constituent of the fibrinolytic enzyme system, is reduced to a few minutes. The concomitant acceleration of plasma-clot lysis is abolished in vivo by the antiactivator e-aminocaproic acid. The inhibiting action of the liver is exercised by inactivation and/or metabolism of the circulating activator or else by release into the blood of antiactivator activity from the liver. This suggests that liver function and thromboembolic diseases might be related (which is not a new concept). Reduction of the circulating activator or strong antiactivator activity, both reflecting an exaggerated inhibitory activity of the liver, lead to reduced spontaneous fibrinolytic activity. Increased antiactivator activity has been found in patients with extended intravascular clotting.3 These observations suggest that the human fibrinolytic system exists permanently in a potentially activated state, It
seems
fibrinolytic activity
and that most of the circulating activator responsible for this potential activation is inhibited through an unknown mechanism by a normally functioning liver. Pathologically increased release of activator into the circulation, known to occur in a variety of circumstances,3 apparently cannot be sufficiently inhibited by the liver and a fibrinolytic reaction results. On this assumption, one might expect that the discovery of the compound which specifically interferes with the inhibitory action of the liver on fibrinolytic activity (much as prothrombin-depressing agents interfere with the synthesis of the prothrombin complex) would open new approaches to the treatment and prevention of thromboembolic diseases. The studies were supported by U.S.P.H.S. grant HE 05538-3 from the National Heart Institute. Department of Medicine,
University of Colorado School of Medicine, Denver, Colorado, U.S.A.
KURT N.
VON
KAULLA.
AN AUTOGENOUS ANTIBIOTIC?
SIR,-It is difficult to believe that the presence of lacticacid-producing microorganisms in mouth and throat, rectum, and vagina is mere coincidence. They have one property in common: they are antagonistic to proteolytic organisms (including certain pathogens) and also to putrefaction. This property has been attributed to the lactic acid produced by these organisms. They produce not only lactic acid, but also hydrogen peroxide.5-’ I experimented with a solution of 3-aminophthal hydrazide described by Langenbeck and Ruge,8 with the modification that I replaced the sodium carbonate used by these workers with an equivalent amount of sodium hydroxide. The results (unpublished) supported the view that the reaction between lactic acid and hydrogen peroxide is an autocatalytic chain reaction. In two previous communications 9 10pointed out that the antimicrobial property of human saliva could be explained by the interaction between the two metabolic products of these organisms-lactic acid and hydrogen peroxide. I was further able to show that hsemin oxidises lactic acid, and that in this reaction peroxide is formed. This could be significant in view of the observation that free lactic acid accumulates in inflamed tissues where free heme compounds are present as breakdown products of leucocytes and erythrocytes." There are probably many other oxidising systems in human tissues capable of inducing secondary oxidation of lactic acid with consequent autocatalytic formation of peroxide. The 5. McLeod, J. W., Gordon, J. Biochem. J. 1922, 16, 499. 6. Bertho, A., Gluck, H. Naturwissenschaft, 1931, 19, 88. as
7. 8. 9.
Fromageot, C., Roux, J. Biochem. Z. 1934, 267, 202. Langenbeck, W., Ruge, V. Ber. dtsch. chem. Ges. 1937, 70, 367. Kraus, A. Lancet, 1962, ii, 664. 10. Kraus, A. ibid. p. 1328. 11. Dubos, R. Biochemical Determinants of Microbial Diseases. Cambridge, Mass., 1954.
chain reaction may also play a part in the hitherto unexplained anti-infective action of ascorbic acid in the body. In the oxidation of ascorbic acid, hydrogen peroxide is formed,11-14 which in the presence of lactic acid could oxidise lactic acid. Jorissen and Belinfante 15 found that ascorbic acid can induce oxidation of lactic acid. Catalase, which may either be present in the tissue
or
be
produced by
the
proteolytic microorganisms
con-
cerned, could by breaking down hydrogen peroxide supply the molecular oxygen necessary to maintain continuous of the lactic-acid/peroxide system.
production
Antibiotics have been defined as " naturally produced inhibitors of the growth of organisms ". If this definition is accepted, the lactic-acid/peroxide system could truly be called an antibiotic produced by lactic streptococci and by lactobacilli. What other function the lactic-acid/peroxide system has in the human body or tissues is not clear. A. KRAUS. Twickenham, Middlesex.
Parliament Legislation
and Addiction
April 30, introducing the second reading of the Drugs (Prevention of Misuse) Bill,16 Mr. HENRY BROOKE, the Home Secretary, said that when an evil was manifestly growing he believed in acting to stop it. Though it had been suggested that legislation was premature, he considered that new powers were needed to deal with the social damage which was being caused by the increasing misuse of drugs, especially the amphetamines. The main purpose of the Bill was to make it an offence to be in unauthorised possession of these drugs and to prohibit their import without a licence. The prescription and sale of these drugs was already controlled by the Pharmacy and Poisons Act, 1933. But when drugs were being traded illicitly, often the only offence it was possible to prove was unauthorised possession, and the police needed additional powers to deal with traffickers in the drugs. Mr. Brooke had been out at night with the police to see for himself the social problems which faced them in Central London, and his visits had convinced him of the need for legislation. He said: " Amid all that sleazy stuff, the thing which impressed itself far the most deeply on my mind was the danger to the teenagers, both boys and girls, if this easy getting and taking of ’purple hearts ’ and pep pills went on growing and spreading." Our weapons for checking it were at present not effective, even with all the help that doctors and pharmacists could give. He asked the House for the new and stronger weapons in the Bill, to save youths and girls from a habit which could become a vice. Mr. ERNEST FLETCHER agreed that some further measures were necessary to deal with the misuse of these drugs. But we should realise that we were taking a novel, if justified, step. The State had always recognised that it had a duty to protect the public in certain circumstances from doing some things which might be harmful to them. That, however, was obviously a principle which one could not carry too far, because if that principle were accepted, one could extend it to the excessive consumption of alcohol, or of tobacco, or of a variety of other matters. We must also not delude ourselves that by passing the Bill we were dealing with the medical and social problems which lay behind the increase in addiction to these drugs. Lord BALNIEL supported the Bill, but also felt that any legislation which created a new criminal offence should be approached with caution. He was concerned that some young people apparently found the real world " so unrewarding and so unsatisfying and unconstructive and unexciting " that they turned to the unreal world of drugs. The Bill was repressive legislation, and repressive legislation almost never ON
12.
13. 14. 15. 16.
Barron, E. S. G., De Meio, R. H., Klemperer, F. J. biol. Chem. 1936, 112, 625. Holtz. P., Triem, G. Z. physiol. Chem. 1937, 248, 1. Schales, O. Ber. Dtsch. chem. Ges. 1938, 81, 447. Jorissen, W. P., Belinfante, F. Chem. Weekblad. 1933, 30, 618. See Lancet, April 11, 1964, p. 835.