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that the drug might have some effect in myelomatosiswhich is also characterised by disturbance in plasmaproteins. SNAPPER 10 has recently reviewed his resultson 35 patients. The drug is given intravenously anda course of 15-20 injections of 150 mg. is needed.The doses are given daily unless there is renal damagewhen they are spaced out to twice a week. Thediet has to be controlled and animal protein kept toa minimum. A troublesome side-effect is a dis-sociated anaesthesia in the area distribution of the

trigeminal nerve, which often appears one to threemonths after the course of treatment. SNAPPERestimates that in four-fifths of his patients bone

pains s were relieved and the disease arrested;" arrest " is the correct term, for X-ray changesremain stationary and serum protein may remainhigh. Most of his patients relapsed within a yearand did not respond so well to second courses ofstilbamidine. Of the 12 patients who had beenunder observation for more than a year after treat-ment, 4 had died and 5 were classed as satisfactoryand were ambulant; 5 of the 8 survivors had livedfor three years since diagnosis and one for six years.SNAPPER and his co-workers showed that in patientswith biochemical evidence of disturbed protein meta-bolism basophil bodies appeared in the cytoplasm ofthe marrow plasma cells when the stilbamidine dose

had reached about 1000 mg. Histochemical and

spectrophotometric studies suggest that these bodiesare composed of ribonucleic acid and stilbamidine.SNAPPER suggests that the myeloma cells containabnormal nucleoproteins in their cytoplasm, and thatstilbamidine has a specific affinity for them. Stilb-amidine is far from the ideal therapeutic agent formyelomatosis, for its action is only partial and it hasunpleasant side-effects, but groundwork for experi-ment has been laid by SNAPPER and we must hopethat more effective compounds will be discovered.If the apparently solitary myelomas are really partof a generalised disease, then the present treatmentby surgical removal and subsequent local radio-

therapy might appear wrong. GOOTNICK 11 has notedthat there are few survivors after ten years. But in

practice there have been many reports of survival forsome years without evidence of general spread, andoperation may be needed to relieve mechanical dis-ability. Perhaps evidence of extensive spread in thesternal marrow should be a contra-indication foroperation.

Here then is another condition in which improveddiagnostic methods have made earlier diagnosispossible, for which effective therapy is being developed.and which is passing over from the surgeon’s to thephysician’s care.

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11. Gootnick, L. T. Radiology, 1945, 45, 385.10. Snapper, I. J. Amer. med. Ass. 1948, 137, 513.

Annotations

PRIVATE PATIENTS NOT ADMITTED

IN a speech reported on p. 515 Mr. Bevan expressedgreat satisfaction at the fact that 92-93% of the popula-tion of Great Britain have already chosen their doctor inthe National Health Service, and said that signaturesare still coming in at the rate of 150,000 a week. Enrol-ment has indeed been far speedier than was expected.In view of the general reluctance to fill in forms of

application for licences, ration books, and the like, itwould not have been surprising if many more peoplehad put off choosing a doctor, or joining his list, untilthe onset of illness made this imperative. Even if therate of new entrants falls steadily from now onwards, itis very likely that by the time the winter illnesses havecome and gone no more than 1 in 40 or 50 will remainoutside the general-practitioner service.

This bears out our contention of a fortnight ago thatthe number of people who might wish to attend healthcentres as private patients -will be very small. Someprivate patients will be under the care of doctors whohave not taken service under the Act ; others will haveelected to remain private patients specifically to avoidever going to see their doctor ; not a few will be elderlypeople, many, of whom are reluctant to change theirhabit pattern or to risk any alteration in their lifelongrelationship with their doctor. When all such are excludedwe are left with an almost negligible proportion of patientswho while remaining private might want to pay anoccasional visit to the health centre. On an averagethrough the country this proportion is scarcely likely tobe as high as 1 % (or 40 patients among the 4000 of a fullyextended practitioner). Though there will of course beareas with abnormally large numbers of private patients,these will seldom be the ones first chosen to have healthcentres.

Nevertheless it seems that the Minister remainsconvinced, as a matter of principle, that private patientsmust be excluded from the use of health centres-even

if this ruling means that the construction of some of theprojected centres will be halted. In this he is supportedby Mr. Somerville Hastings. The Times on Sept. 10 said :

‘ The doctors have been told that they must not seeprivate patients at a health centre provided by the localauthority. This is a blunder. Specialists are to be allowedto carry on private practice at State-provided hospitals:yet general practitioners are to be denied similar privilegesat State-provided health centres. All private patients areperfectly cligible to benefit from the facilities of the healthservice and, as taxpayers, they are part-owners of the buildingsin which the work of the service is done. Why should theynot pay for what in any case they are entitled to get free ? ?’’

Mr. Hastings on Sept. 15 replied that if the privatepatients " are intelligent people, they would only ask tobe seen privately and pay for it if they expected to receiveeither preferential, more considerate, or better treatment.And this is what they would be bound to get, so that.there would be two standards of treatment in the samehealth centre." But is this theoretical reasoning supportedby experience ? In actual fact people who have electedto remain private patients still seem to be content toattend for some services at their doctor’s surgeries, andask there no preferential attention, nor any more con-siderate or better treatment than that being given to hisState-enrolled patients. The truth seems to be that the

great majority of patients remaining as private patientsdo so in order that they may suit their own convenienceas to when, where, and how. often, they consult theirdoctor. For certain services (e.g., recurrent injections,minor dressings, vaccinations, ear syringing, the renewalof priority certificates, or the obtaining of signatures forpassports and other documents) it generally suits privatepatients to come at a fixed, and early, time to their doctorrather than wait indefinitely at home for his arrival.Why should they not seek similar services in a healthcentre ? g No more than now will they need or ask anyspecial attention.

If a doctor had any substantial number of private,patients, the fact that these were denied entry to thehealth centre might in the end prove prejudicial to his

501

public practice, however good his intentions. He mightbe obliged to hold a surgery at his own home beforeproceeding each morning to the centre, and this mighteasily cause a waste of time through which his day’swork would suffer.Mr. Hastings very rightly wants to avoid two standardsof treatment inside the health centre. But by excludingthe private patient is he not in danger of fostering theidea that something better, or something more con-

siderate, can be provided for the private patient at thedoctor’s own surgery ? f Surely our aim is to provide thebeat possible conditions for practice inside the healthcentres. We want this to be recognised alike by doctorand patient. We shall not teach any patient the value ofhealth centres by denying him entry to them. We shall-not enhance the- attraction nor increase the efficiency ofthe centre by carving on its lintel " No admittance forPrivate Patients." Once the centres are provided, wemust use them to their greatest advantage-use themespecially to save the doctor waste of time and effortso that his energies may be utilised to the full. The Actallows the patient the right to obtain privately any sectionhe chooses of his medical care, and expressly permits thepractitioner to give private attention to patients whoinsist on having it. Anomalies are bound to arise throughthis very provision. But the more we try to keep separatethe care of the two groups of patient, the greater thedifficulties we create for ourselves and the greater thewaste of man-hours we cause. In any case we could not

carry the separation to a logical end without arriving ata ludicrous conclusion. If we exclude the private patientfrom the centre in person, must we also prevent his doctorfrom testing in the centre his blood, his urine, or anythingthat is his ? Must telephone calls to the doctor be refusedat the centre if they concern private patients ? Indeed,may the doctor even ponder the problems of a privatepatient, or discuss them with a colleague, once he isinside the portals of the centre ? Each and every one ofthese things he can do, or have done, for his patient atthe State-provided hospital: why not at the State-provided centre ? ’?

Feeling, as we do, that there is no logical or justlycalculable point at which a line of division could bedrawn, and confident that numerically the demandsmade on the centre by the private patient will notbe great and will not in practice necessitate any discrimi-nation between the two types of patient, we still believethat in the first experimental centres doctors should notbe forbidden to treat those private patients who elect toattend there. The day-to-day experience of these centreswill be far more valuable than any present postulation ;and, if our contentions are proved wrong, and the smoothrunning of these early centres founders on the rock ofclass discrimination, it will then be time enough to tryinstead the feasibility of making the doctor segregatehis patients -and conduct his practice in duplicate fromtwo separate establishments. Time enough, if our

present opportunity has not itself been lost throughdisagreement, discouragement, and delay.

RADIOACTIVE PENICILLIN

THE prospect of growing supplies of radioactive isotopes,announced in these columns last week (p. 469), opensup an exciting and obviously fertile field for pharmaco-logical and physiological research. It is 25 years sinceHevesy 1 first applied isotopes to the study of plants,using radioactive lead. In the early experiments onlynaturally occurring radioactive substances could beused and the scope of this powerful weapon of investiga-tion remained strictly limited until a method for pro-ducing radioactive isotopes artificially was discovered

1. Hevesy, G. Biochem. J. 1923, 17, 439.

by Joliot-Curie and Joliot 2 in 1934. In 1932, Urey and hiscolleagues discovered deuterium (H2) and soon developedpractical methods for the production of highly con-

centrated " heavy water." In the next desade radio-active isotopes of nitrogen, carbon, sulphur, phosphorus,iron, and many other elements were produced. In a

relatively short time, therefore, a wealth of isotopictools became available for the elucidation of physiologicaland biochemical problems which had previously defiedsolution. Much interesting information was soon

gathered. Using radioactive sulphur, for instance,Tarver and Schmidt 3 showed that in normal metabolismthe sulphur of cystine is derived, at least in part, frommethionine, but not from elementary sulphur or fromsulphate. Radioactive isotopes of iron have been usedby Whipple and his associates 4 in biochemical andphysiological studies of erythrocytes. A fascinatingaspect of isotope research is the determination of thesteps in the breakdown or synthesis of biologically_ important products by the organism. An isotope ofphosphorus, P32, has been used for the study of

phospholipid, nucleoprotein, and carbohydrate meta-bolism, while thyroid function and iodine metabolism,including the role of the pituitary thyrotropic hormone,have been studied with 1.

Thus, starting from naturally occurring radioactivelead, through the induced radioactive isotopes of manyelements, organic substances have been built up contain-ing radioactive carbon, nitrogen, phosphorus, or sulphur,and these have provided us with agents for probing themysteries of intermediate metabolic processes in bio-

logical systems. The latest application of this techniqueis in penicillin research, where the mould is made to

incorporate a sulphur isotope into the penicillin molecule.Rowley and colleagues,5 while investigating the glutamic-acid uptake by bacteria, used a preparation of radio-active penicillin, made by inoculating a synthetic brothmedium containing S35 with a vegetative culture of theQ176 strain of P. chrysoyenum, in which the sulphurcontent had been reduced to a point at which it becamethe limiting factor in the yield of penicillin. The yieldfrom 2 ml. of broth was 250 i.u., representing a 12 % con-version of the sulphur in the broth into penicillin with aspecific activity of 0-05 microcurie per i.u. It was notedthat the presence in the medium of 50 millicuries of S35per litre did not adversely affect the growth of the mould.A preparation of radioactive penicillin with a muchweaker activity has recently been reported 6 from theUnited States. With their radioactive penicillin Rowleyet al. demonstrated that the absorption of penicillin,if any, probably amounts to less than 10 molecules perbacterium (Staph. aurecs).

Extending this work on penicillin labelled with S3f>,Rowlands, Rowley, and Stewart, in this issue, reportsome excretion and absorption studies in cats. Bygiving mixed ordinary and labelled penicillin intra-

’ muscularly they found that 100% of the radioactivesulphur isotope was excreted in - the urine, but the

recovery of biologically active penicillin was much less.There was no evidence of any retention in the body, asthe radioactive breakdown products (at present unknown)were excreted over the same interval of time as the

penicillin itself. In a previous study of the absorptionof penicillin given by mouth, Stewart and May 7concluded that " the most important factor influencingthe absorption of penicillin seems to be the unexplained2. Joliot-Curie, I., Joliot, F. C.R. Acad. Sci., Paris, 1934, 198, 254.3. Tarver, H., Schmidt, C. L. A. J. biol. Chem. 1939, 130, 67.4. Hahn, P. F., Balfour, W. M., Ross, J. F., Bale, W. F., Whipple,

G. H. Science, 1941, 93, 87.5. Rowley, D., Miller, J., Rowlands, S., Lester-Smith, E. Nature,

Lond. 1948, 161, 1009.6. Howell, S. F., Thayer, J. D., Labaw, L. W. Science, 1948,

107, 299.7. Stewart, H. C., May, J. R. Lancet, 1947, ii, 857.