59

Gamma-globulin in Measles

THE LANCETLONDON: SATURDAY, JULY 10, 1948

GAMMA-DI.OBUMN IN lBfEARLES

ANTIBODIES, as has long been known, reside mostlyin the globulin fraction of the blood. Modern methodsof fractionating the plasma proteins, as by electro-phoresis and ultracentrifugation, have shown that theantibody is concentrated particularly in the gamma-globulin which constitutes about 11% of the total

protein. When, early in the war, E. J. CoHN and hiscolleagues. at Harvard undertook the large-scalefractionation of human plasma by alcohol precipitationin the cold, with the primary object of supplyingalbumin for combating shock, they naturally usedthe same methods to separate the other proteinmoieties like fibrinogen and the globulins. Eventually,a viscous substance called fraction n, containingabout 16% protein as practically pure gamma-globulin and with the natural antibodies concentrated20- to 30-fold, was submitted to clinical trial. Wholeblood, normal adult serum; and convalescent serumhave all been used with varying success in the

prevention or attenuation of measles, and the newgamma-globulin was therefore first tried in thisinfection. The results were astonishingly good ; notonly was the disease prevented or attenuated bysmall doses given early in the incubation period,but it was even claimed that the rash could be abortedwhen larger doses were given in the prodromal stageof infection.The method of fractionation elaborated by the

Harvard workers, involving such variables as pH,salt concentration, protein concentration, and theuse of alcoholic solvents at a temperature range of0 to - 10°C, could not readily be used extensivelyin Britain during the war. When, therefore, a giftof a litre of gamma-globulin was received from

America in 1943, a small working party under thechairmanship of Sir PERCIVAL HARTLEY was set upto organise carefully controlled trials with the preciousmaterial. Their results are reported at the front ofthis issue. It was known from earlier experience,particularly in the London County Council fever service,that convalescent measles serum would protect a highproportion of contact children, aged 6 months to5 years, if given in doses of 5-10 ml. within five tosix days of exposure to measles ; so this first batchof gamma-globulin was used in a comparative trialwith convalescent measles serum on groups of sus-

ceptible children intimately exposed to infection inhospital, in day or residential nurseries, or in theirown homes. The results in 139 children given gamma-globulin and a comparable group of 136 children givenconvalescent serum showed that the concentratedglobulin was about twice as potent as the convalescent

serum. Thus, in the most susceptible age-group ofchildren aged 1-4 years, only 2 out of 28 given2’5-3’5 ml. of globulin developed (mild) measles,compared with 7 out of 33 children given 5 ml.or more of convalescent serum. In contrast withearlier experience with placental globulins, there wereno local or systemic reactions although the viscoussolution had to be injected with a needle of fairlywide bore.With the demonstration that gamma-globulin was

both safe and effective, subsequent trials with freshsupplies received from America were devised to assayappropriate dosage for prevention or attenuation, tocompare the potency of different batches, and toassess the keeping qualities of the antibody in liquidsolution. When a dose of 0’1 ml. per lb. body-weightwas used, a protection-rate of 92’6% was obtained fromthe sum of 13 different batches of globulins ; 4 of the5 unprotected children in this group developed mild .

measles. While the figures are too small to allowcomparison of the potencies of different batches,there was at least one batch of low-potency globulin(omitted from the analysis above) which protectedonly 16 out of 28 children in the standard dosageof 0’1 ml. per lb. body-weight. Whatever was thecause of this deficiency, it seems unlikely, in a highlyurbanised community where 80-90% of childrendevelop measles, that concentrated globulin from poolsof adult serum will vary much in their content ofmeasles antibody. When attenuation rather than

protection is desired, the American workers haverecommended a quarter of the protecting dose, butthe present study and experience with convalescentserum suggest that about half the standard doseshould be used. Potency seemed to be maintainedfairly well in the liquid preparation kept in cold

storage for two years or more, though it should benoted that in the highly susceptible age-group of1-4 years, 22 out of 110 children given " protective "doses of the outdated globulin developed measles.It would be wise, therefore, to freeze-dry batches ofglobulin that may have to be kept for some timebefore use. ’

Measles is not the killing disease it was even aslate as twenty years ago, but it may still be a seriousinfection in’ young children and lead to cripplingcomplications like otitis media and bronchopneumonia.Most doctors would therefore prefer to abort or

attenuate the attack in susceptible children of 6 monthsto 3 years of age known to be exposed to infection.The supply of convalescent serum is always verylimited ; normal adult serum may modify but notusually prevent an attack unless given in large doses,and there is the small risk of homologous serumhepatitis. Concentrated globulin in amounts of2-3 ml. will either give temporary protection or willso modify the attack that the risk to the child isminimal. And there has been no recorded instanceof homologous serum hepatitis after many thousandinjections of gamma-globulin. The main problemfacing us is the large-scale supply of this commodity.The raw’ material will probably be obtainable insufficient amount through the National Blood Trans-fusion Service. A method of concentrating the

antibody-containing globulins, using precipitation withether instead of alcohol; has been developed by

60 A TAX ON KNOWLEDGE

KEKWICK and his colleagues 1 at the Lister Institute,and already experimental batches of this globulin arebeing tested in controlled clinical trials with encourag-ing results. Meanwhile, until supplies become moregenerally available, normal adult serum, which is

. distributed by the Public Health Laboratory Service,may be used in doses of 5-10 ml. to modify theattack in young children.

There are other uses for gamma-globulin. It has

already proved effective in the prophylaxis of infectivehepatitis, and has even had some success againstupper respiratory infections.2 Like other preparations,it has failed to abort the paralytic stage of polio-myelitis and has given negative results in the controlof chicken pox and mumps. Here it may be necessaryto prepare a concentrated globulin from pools ofconvalescent serum ; in one study 3 such a globulinapparently reduced the incidence of orchitis whengiven in doses of 20 ml. after the onset of mumpsin young adults. We do not yet know whether it willprotect the pregnant woman against rubella; butwe can fairly hope that this substance, originally almosta waste product, will prove an effective new weaponagainst the still intractable virus infections.

A Tax on KnowledgeFROM time to time attention is drawn to the dis-

couraging attitude of our income-tax law towardssuch professional expenses as the purchase of text-books -and scientific journals and subscriptions tosocieties. A correspondent serving in the Forces

complains that no rebate is allowed him in his effortsto use these means of keeping abreast of currentmedical knowledge on a fixed salary. He suggeststhat a medical man in the Services is in this respectdenied privileges which civilian doctors enjoy. Butsubject to the mysterious distinctions discoverablein the expense rules under schedules D and E, it doesnot appear that civilians obtain much greater advan-tage from the Inland Revenue than doctors servingin the Navy, Army, or Air Force.The material passage for the latter seems to be

found in schedule E, which charges tax " in respectof every public office or employment of profit." Rule 9of this schedule allows a deduction of expenses"

necessarily incurred and defrayed " in travelling

in the performance of the duties of the office or

employment or " (a pleasant old-world touch) " keep-ing and maintaining a horse to enable him to performthe same," or otherwise spending money " McHexclusively, and necessarily in the performance of thesaid duties." No-one, of course,-expects the InlandRevenue to be soft-hearted in applying these wordswhich we have italicised. An air pilot was not allowedto deduct the cost of a telephone to his house. Thenearest case for our present purpose is Simpson v. Tatewhere in 1925 Mr. Justice ROWLATT held that a

county medical officer was not entitled to deductthe cost of subscriptions to medical and other pro-fessional societies. " I think," said the learned

judge, " that all subscriptions to professional societies1. Kekwick, R. A., Record, B. R., Mackay, M. E. Nature, Lond.

1946, 157, 629. Kekwick, R. A. Proc. R. Soc. Med. 1947-48,41, 217.

2. Adams, J. M., Smith, H. Proc. Soc. exp. Biol., N.Y. 1946,63, 446.

3. Gellis, S. S., McGuinness, A. C., Peters, M. Amer. J. med. Sci.1945, 210, 661.

and all taking in of professional literature and allthat sort of expense which enables a man to keephimself fit for what he is doing are things which cannone of them be allowed. If they were allowed, everyprofessional man would say: ’I have to belongto this and I have to belong to that society ; I haveto take in this publication and I have to take in thatpublication, and to do all sorts of things,’ and therewould be no end to it. I think the principle is quiteclear ; nothing of that sort can be allowed." Thelatest edition of Judge KoNSTAM’s Law of IncomeTax observes that this decision seems doubtful. Itwas followed nevertheless in 1945 in Blackwell v. Millswhere there had been a condition in an employee’scontract of service that he should attend classes atthe Chelsea Polytechnic ; the expense of the classeswas not allowed as a deduction. One other case isworth noting-Wales v. Graham, in 1941. Here the

taxpayer, a divisional engineer employed by theLondon County Council, sought to deduct the costof his subscription to the Institution of Civil Engineers.Candidates for the post of divisional engineer had tobe corporate members of the institution or to holdqualifications approved as equivalent. It was not

specifically required that membership of the institu-tion should be continued after the candidate was

appointed, but there was substantial evidence thatrelinquishment of membership would make impossiblethe continued efficient discharge of the full duties ofthe office. The Crown argued that the subscriptionto the institution was not money expended wholly,exclusively, and necessarily in the performance of thetaxpayer’s duties : it was not enough to show that itwas " necessarily " incurred to secure or retain theappointment or to obtain promotion in the service.The court refused to allow the deduction.

Private practitioners are assessed, of course, underschedule D of the Income Tax Act and not underschedule E. This seems to permit a slightly moregenerous attitude. Where schedule E speaks ofsums " wholly, exclusively, and necessarily expendedin the performance of the duties of the office or

employment," schedule D speaks of sums "whollyand exclusively laid out or expended for the purposesof the trade or profession." Significance is attachedto the word " necessarily " in schedule E and to thewords " purposes of the profession " in schedule D.There seems no reason why the expense rules shouldbe more niggardly in the one case than in the other.Practitioners in medicine and surgery who serve inH.M. Forces are not unreasonable in thinking them-selves at some disadvantage in their efforts to keepabreast of current developments. Their anxiety togive of their best should not be taxable. ,

Among the expenses " necessarily and reasonablyincurred " by specialists " in the course of their

work," the last Spens Committee includes " thecost of books and journals, preparation of scientificpapers, and subscriptions to professional societies " ;and it presumes that the Inland Revenue authorities" would be prepared to consider favourably as

legitimate allowances for income-tax purposes anyitems of expense which had been approved by apublic hospital authority." We hope that theMinister of Health may indeed be able to persuadethe Treasury to take this wise view.

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