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sugar moieties, the bases being adenine, guanine, cytosine,and thymine, while the sugar was desoxyribose., Thepolymerisation can be represented as:

This synthesis took place only in the presence of somealready polymerised material such as desoxyribonucleicacid (usually called the primer), and, after painstakingpurification of his enzymes, Kornberg showed thatthe amount of polymeric material at the end of his

experiment was clearly greater than the amount of primerhe had started with. Here again, the product was chemi-cally, physically, and enzymically indistinguishable fromnatural desoxyribonucleic acid.

Protein synthesis is widely thought to be controlled bythe genic material of the cell, desoxyribonucleic acid,acting through the ribonucleic acid, and it seems likelythat the order in which the four common bases are

arranged in the ribonucleic acid must be dictated by thegenic material, and that the order specifies, in some formof code, the order in which the various natural aminoacidsare built into new protein. Investigations in this fascinat-ing field have been handicapped by the difficulty of

isolating undegraded nucleic acids (especially the ribo-nucleic acids) from the cell, but, now that the work ofOchoa and Kornberg has made available similar polymersmade under controlled and reproducible conditions,progress in the mechanism of protein synthesis, and itsrelation to normal and abnormal metabolism, seems morepossible.

GONORRHOEA

AT its first meeting, in January, 1948, the W.H.O.Expert Committee on Venereal Diseases recommendedthat " international V.D. activities should place majoremphasis upon the detection and treatment of earlysyphilis ", remarking that " antibiotic therapy appears tohave transformed gonorrhoea from a disease of greatchronicity with frequent recurrences, with great tendencyto troublesome complications and protracted disability toan infection readily amenable to treatment and withalmost complete freedom from complications or tendencyto relapse." At its fifth meeting, held in Geneva lastmonth, the committee was presented with figures showingthat in 22 countries the annual number of cases of

gonorrhoea since 1950 had fallen in only 4, had stayedstationary in 2, and had risen in 16.Though there seems to be ample evidence that peni-

cillin has been " losing its punch " against certain strainsof gonococci, the great majority of infections still respond

to generous treatment: the recent worsening of results insome parts of the United Kingdom has not been matchedin the United States, where for some years now gonorrhoeahas been treated with penicillin in large enough dosageto abort a hypothetical incubating syphilitic infection.

Despite the rise in new cases-and in this country ithas been considerable-there is still no evidence of anincrease in those crippling complications which madegonorrhoea such a serious public-health problem in thedays before specific treatment was feasible. There is,however, no guarantee that such an increase will not

occur; and the committee considers that the whole ques-tion of gonorrhoea, particularly its diagnosis and treat.ment, should be taken up internationally by the creationof a W.H.O. gonococcus centre to collaborate withnational laboratories throughout the world.

Penicillin, though it has been outstandingly successfulin the control of the non-venereal treponematoses, andindeed of the venereal type, has on the whole had adisappointing impact on the incidence of gonorrhoea.This is largely due to faith in one-shot treatment, withfailure to recognise that infectious latency, especially inwomen, is still a feature of the disease. The diagnosis ofgonorrhoea in its latent stages is difficult, and the tradi-tional stained films and cultures are no less imperfectfor this purpose than they always have been.

LONG-TERM PROGNOSIS IN EPILEPSY

THOSE who undertake the long-term care of epilepticpatients know that the frequency of their attacks may varywidely from time to time in an unpredictable and seem-ingly causeless manner. This greatly increases the

difficulty of assessing the results of treatment andemphasises the need for long-term surveys. The effectsof surgical treatment are best evaluated when a post-operative period of at least five years can be comparedwith a similar time before operation.

This spontaneous variation may also give rise to a

healthy scepticism about medical treatment. Thus a

patient may have a number of fits in childhood or ado-lescence. He is put on to an anticonvulsant regime, andin a few weeks or months the attacks largely cease. The

regime is continued with apparent success; but in thefifth or sixth decade, perhaps with evidence of mildcerebrovascular change, or earlier with no apparentprecipitating factors, the attacks recur. What evidencehave we that in the intervening years the anticonvulsanttreatment has been responsible for the absence of fits?Why should it not have been due to the spontaneousvariation which we know occurs ? Since both clinicaland electrical evidence suggest that epileptic firing is

episodic, we must assume that medical therapy is a

somewhat blunderbuss affair; and that we should try todiscover what factors are likely to initiate or enhance suchfiring, and then, if they are unavoidable, to apply treat-ment at times of risk.

This problem has led some physicians to try a periodicreduction of drugs to see whether the frequency ofattacks is affected. The majority, however, prefer not toalter a regime on which the patient is having few or nofits. When anticonvulsants are abruptly stopped, attacksmay be induced which would not have occurred if thebrain had never been subjected to the drugs. Neverthe-less, there is something to be said for periodic gradualreduction of drugs. After all, no drug should be exhibitedunless it is producing the effect for which it is intended;and the known and clinically overt hazards of protracted

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1. Strobos, R. R. J. A.M.A. Arch. Neurol. 1959, 1, 216.2. Merritt, H. H. Brit. med. J. 1958, i, 666.3. Epidem. vit. Stat. Rep. World Hlth Org. 1956, 9, no. 4.4. Dreyer, K. Damsh med. Bull. 1959, 6, 65, 75.5. Swinscow, D. Brit. med. J. 1951, 1, 1417.

treatment with anticonvulsants are not negligible: the

subliminal effects on cerebral efficiency are largely un-assessed ; and when patients themselves mention possiblesymptoms they are usually dismissed as psychogenic.With these questions in mind Strobos 1 observed the

results of medical treatment in 228 patients with " idio-pathic " epilepsy for periods of from two to fifteen years.86 were completely controlled; in 41 of these an attemptwas made to reduce medication, but 19 had a recurrenceof attacks. Merritt 2 referred briefly to similar findingsin 85 cases of patients with completely controlled attackswho had their drugs gradually reduced. He did notmention the period of observation, but no less than 29remained seizure-free when off all medication. Undoubt-

edly detailed reassessment of medical therapy would beof value; and we should seek to define the effectivenessof the various medical treatments in terms of decadesrather than years. The opportunity could also be takenfor renewed observations on the " natural history " ofepilepsy.

COMPARATIVE SUICIDE STATISTICSTHE incidence of suicide has increased in most

countries since the late war, and, with the decrease in thedeath-rate from other causes, suicide now accounts for a

higher proportion of deaths, especially among young andmiddle-aged people. A World Health Organisationpublication 3 giving comprehensive statistics on mortalityfrom suicide in various countries drew attention to the

comparatively high rate in Denmark; and Dreyer 4 hasnow examined the Danish figures from 1835. A hundredyears ago the crude suicide-rate in that country was

higher for males than it is now, and it was about the samefor females. The Danish suicide-rate in the 19th centurywas among the highest in Europe, and Denmark is stillnear the head of the list. For males, the Danish suicide-rate at the turn of the century was equalled only bySwitzerland (about 40 per 100,000 population). TheDanish male suicide-rate decreased during the first decadeof this century and, as in most other countries, it decreasedstill further during the first world war, rising thereafterthough not to its 1900 level. In the 1939-45 war the ratesin males decreased at first in most countries; but in theoccupied countries considered (Norway, the Netherlands,Denmark, Finland, and Belgium) the rates either increasedor were irregular towards the end of the war. There wasalso a slight rise in male suicide-rates from 1942 onwardsin England and Wales. After the war the suicide-rate

among males in Denmark rose to 32 per 100,000, at whichlevel it remains. The suicide-rate among females inDenmark began to rise in 1928, and it rose still moreduring the 1939-45 war (from 10 per 100,000 in 1939 to24 per 100,000 in 1945). The sex ratio for suicide inDenmark and most European countries was 3 or 4 malesto 1 female in the latter part of the 19th century, but inDenmark the increased number of female suicides haskept the ratio at about 2 to 1 since 1950.Dreyer analyses the Danish age-specific suicide death-

rate, comparing it with the corresponding rate for Englandand Wales. Swinscow found that in England and Walessuicides under the age of 55 included a relatively highproportion of females, but the Danish figures showno such trend, except in the late war; and, whereasSwinscow found that the proportion of all suicides

1. Harrison, H. E., Harrison, H. C. J. clin. Invest. 1955, 34, 1662. SeeLancet, 1957, ii, 630.

2. Albright, F., Sulkowitch, H. W., Chute, R. J. Amer. med. Ass. 1939,113, 2049.

3. Boothby, W. N., Adams, N. Amer. J. Physiol. 1934, 107, 471.4. Kissin, B., Locks, M. O. Proc. Soc. exp. Biol., N. Y. 1941, 46, 216.5. Scott, W. W., Huggins, C., Selman, B. C. J. Urol. 1943, 50, 202.6. Shorr, E. ibid. 1945, 53, 507.7. Robinson, R. H. O. B. Proc. R. Soc. Med. 1947, 40, 201.8. Conway, N. S., Maitland, A. I. L., Rennie, J. B. Brit. J. Urol. 1949,

21, 30.9. Vermeulen, C. W., Lyon, E. S., Miller, G. H. J. Urol. 1958, 79, 596.

10. Yarbro, C. ibid. 1958, 80, 158.11. McGeown, M. G. Clin. Sci. 1959, 18, 185.

accounted for by the younger age-groups was falling,Dreyer finds that the proportion (except during and justafter the war) remains more or less constant.

In addition to sex and age, Dreyer considers seasonand method. A table of seasonal distribution from 1835to 1955 shows a peak rate in the early summer months(May to July) and a smaller peak in the autumn in mostperiods; but these seasonal variations have been less

pronounced in recent decades. Seasonal graphs given bySwinscow for England and Wales for the three decadesfrom 1921 show a similar peak slightly earlier in the year,with a tendency to higher rates in the end months but anarrower range of fluctuation. As regards method, Dreyershows that since the 1940s male Danish suicides have not

changed their methods but that there has been a consider-able fall in the percentage of females using poison with acorresponding increase in drowning and hanging.

FORMATION OF RENAL CALCULI

THE administration of acetazolamide to rats has beenshown to decrease the urinary excretion of citrate and topromote deposition of calcium in the kidneys.1 Albrightet al. had previously used the solvent effect of citrate oncalcium to attack urinary calculi in vivo by lavage of thebladder or renal pelvis with buffered citrate solutions.Absence of citrate in the urine of patients with calculi wasfirst noted by Boothby and Adams 3; and a similarobservation was later reported by others.4 5 Shorr 6 con-sidered that the absence of citrate from the urine, withconsequent failure to hold calcium in solution, was anxtiological factor in the production of calcium stones.Since in women excretion of citrate increases duringovulation and in either sex a similar increase can beobtained by administration of cestrogen, Shorr suggestedthat this hormone might be administered for treatment ofpatients with urinary stones; and Robinson reviewedthis treatment with approval. Conway et al.,8 on the otherhand, failed to confirm that deficient renal excretion ofcitrate was important in the formation of renal calculi.They believed that any gross diminution of urinarycitrate was due simply to infection of the urinary tract.Experiments in vitro confirmed that the organismscommonly present in infected urine destroyed citrate.

Nevertheless, the view that calculi are formed becauseof a deficiency of some substance, normally present inthe urine, which binds calcium to form a soluble complexis an attractive one. It would explain the " supersatura-tion " of the urine with calcium-a concept which hasbeen generally accepted, and which has been upheld bysolubility studies.9 10 Dr. Mary McGeown,ll of Belfast,has now brought forward evidence which suggests that thechelating agents are the urinary aminoacids. She examinedtwenty-four-hour collections of urine from 110 patientswith calcareous renal calculi and from 29 healthy people.The mean urinary aminoacid nitrogen in the control groupwas 322-9 mg. and in the patients 235 -0 mg. per twenty-fourhours. Only 2 of the 29 controls, compared with 44 of the110 patients excreted less than 200 mg. No difference in