826 BIOTIN

contents. With this. new concept, LOVELOCK andhis co-workers argued that condensation of theatomised or volatilised antiseptic on the bacteria-

carrying particles would be favoured by its havinga low vapour pressure so that saturation of the

atmosphere could be readily achieved ; water-

solubility so that the antiseptic would dissolve inthe moisture of which the particle is mostly composed;and stability in the air for continuity of action.On this basis, they have tested a number of hydroxyacids, among them lactic acid which in a concentrationof 01 mg. per cubic foot proved to be a remarkablyeffective aerial antiseptic over a wide range of relativehumidities (30-80%). Humidity is an importantfactor in the efficiency of different aerial disinfectants :thus propylene glycol is most rapidly lethal at arelative humidity of 60% ; triethylene glycol at

35-45% ; and resorcinol at 75%. The resistance ofdried saprophytic bacteria to disinfectant mists mustnot be regarded too seriously, for hypochlorite, theglycols and lactic acid are all quickly lethal to

bacteria-carrying droplets freshly sprayed from therespiratory tract, as well as to finely atomised bacteriaand viruses sprayed into an experimental chamber. -

As regards field trials, HARRIS and STOKES 10 in awell-controlled experiment found a remarkable reduc-tion of colds in a children’s convalescent home fromthe use of propylene and triethylene glycol. But, asBOURDILLON commented at the RSM discussion, thereare still many obstacles to practical trials of aerialdisinfectants on a large scale in this country, includ-ing the lack of sustained interest, the trouble and-expense involved, the elusiveness of viruses, the diffi-culties in the way of properly controlled tests. Yet

opportunities there are in plenty ; in hospitals, schools,cinemas and barracks. For sudden large-scale epide-mics such as an outbreak of influenza, BOURDILLONrecommends the use of hypochlorite for continuoususe on a smaller scale-e.g., in hospitals or cinemas-UV light, the glycols (difficult to obtain at present),or lactic acid would be more suitable. These new

concepts and methods encourage the hope that wemay be on the threshold of an attack upon the

respiratory diseases similar in its consequences tothose that the water-carriage system of sewage disposalhad upon the intestinal infections.

BIOTINTHE existence of vitamin H or biotin has been

recognised for some forty years, but it is only com-paratively lately that its properties have becomeknown in any detail. The story of this newly charac-terised substance is a striking example of the way inwhich seemingly unrelated researches may, supple-ment one another.

In’1901 WILDIERS observed that for satisfactorygrowth many yeasts and other micro-organisms re-quire a factor,

"

bios," absent from ordinary syntheticmedia but present in extracts of most plant and animaltissues. In 1923 this bios was shown to be a complexgrowth factor, and in the next year LUCAS 11 separatedit into bios i and bios 11. In 1928 EASTCOTT 12 isolatedbios I in the pure crystalline state and identified it asthe long-known i-inositol. Later bios 11 itself was

9. Lovelock, J. E., Lidwell, O. M. and Raymond, W. F. Nature,Lond. Jan. 1, 1944, p. 20.

10. Harris, T. N. and Stokes, J. Amer. J. med. Sci. 1943, 206, 631.11. Lucas, G. H. W. J. Phys. Chem. 1924, 28, 1180.12. Eastcott, E. V. Ibid, 1928, 32, 1094.

shown to be a complex, of which one component,biotin, was first isolated by KoGL and Torrrms 13 in1936 ; their raw material was dried yolk of ducks’eggs, from .250- kg. of which they obtained only 1-1 mg.of crystalline biotin. For twenty years previouslyother workers had been engaged in what was appar-ently quite another field.. BATEMAN in 1916 notedthat egg-white has a definite toxicity if included in °

large amounts in the diet of animals, and in 1927BOAS 14 described the so-called egg-white injury. In1931 GYÖRGY recognised the necessity of an anti-egg-white-injury factor for man, proposing the namevitamin H, and in 1940 DU VIGNEAUD and his colla-,borators demonstrated the identity of vitamin Handbiotin. Since then rapid progress has been made inthe chemical investigations. In 1942 convincingevidence for the structure of biotin was put forward,15and within the past year this has been confirmed bysynthesis of biotin in the laboratories of Merck and Co.Inc. in America. It consists essentially of a reducedthiophene ring bearing a valeric acid side-chain andfused with a molecule of urea to form a second

heterocyclic ring.Although the chemical study of biotin is now very

complete, its physiological properties are still not

fully understood. It is essential to the growth of awide range of micro-organisms and can act in very highdilutions ; thus by using suitable test organisms,such as Saccharomyces cerevisiae, dilutions as great asone part in 400,000,000 can be both detected andmeasured. Many bacterial species and several mouldspossess, or can acquire, the power of synthesisingbiotin ; these include strains of Mycobacteriumtuberculosis, Bacillus anthracis and Staphylococcus -

aureus.. For many micro-organisms biotin from .

which the sulphur has been removed (desthiobiotin)appears to be as effective as biotin itself, probablybecause they can change it back to biotin. Organ-isms in the rumen of cattle have been shown to be

capable of synthesising biotin and the intestinal flora ofother animals may also possess this power. The egg-white injury demonstrated in rats is not a direct toxiceffect but the result of biotin deficiency, for egg-whitecontains a protein constituent, avidin, which readilycombines with biotin and renders it unavailable to the

body. The consequences are typically a dermatitis ofseborrhoeic desquamative type, accompanied by de-nudation of the hair around the eyes-the

"

spectacleeye." Unless the condition is of long standing thesymptoms can be quickly cured by administration ofbiotin, but continuing deficiency leads to great emacia-tion and death. In chicks analogous signs are seen.While biotin is undoubtedly essential for man as

well as for animals, information on human require-ments and the effects of deficiency is still scanty.The reason no doubt is that this vitamin is widelydistributed in food and resists most cooking processes,while tiny quantities suffice to maintain health. It is

found, in very small amounts, in the tissues of all

higher animals, and especially in liver, kidney, eggs andmilk. Trypsinised liver contains of the order of 1800millimicrogrammes per gramme dry weight, and milkroughly 10 millimicrogrammes per millilitre. It hasbeen reported that the biotin content of tumour tissueis generally higher than that of normal tissue of the

13. Kögl, F. and Tönnis, B. Hoppe-Seyl. Z. 1936, 242, 43.14. Boas, M. A. Biochem. J. 1927, 21, 712.15. du Vigneaud, V. Science, 1942, 96, 454.

827MITE versus MAN

same type, but the significance of this is uncertain.Since the vitamin is also widely distributed in the

plant kingdom, all ordinary diets contain adequateamounts. No clear-cut cases of acute spontaneousdeficiency seem to have been described, and it is

probable that the- condition will develop only inassociation with other vitamin deficiencies-e.g., inchronic alcoholics and others living on unnatural diets.

. SYDENSTRICKER,16 however, is able to report someinteresting observations on four human volunteers inwhom biotin deficiency was induced by a diet inwhich 30% of the calories were supplied by egg-white.All other known vitamins were supplied in adequateamounts. After 3-4 weeks the subjects developeda striking ashy pallor of the skin and mucous mem-branes, followed by a branny desquamation. Ex-treme lassitude, muscular pains and anorexia werealso noted. Blood changes recorded included a

reduction in red cells, a slight rise in bile pigments anda considerable rise in serum cholesterol. Parenteraladministration of biotin removed the symptomsspeedily. It appeared that the minimum quantitynecessary to maintain relief was 150 ju.g daily, and atpresent this appears to be the only available estimateof human requirements.Vitamin H therapy is said to have been successful

in a few cases of acne vulgaris 17 and of furunculosis.Recent accounts in the popular press have attributedto biotin remarkable powers of restoring lost hair, butthe facts indicate only that certain cases of baldness inmen, arising from seborrhcea, have benefited from itsadministration. The vitamin has also been used,though with doubtful advantage, in the treatment ofother skin diseases. As supplies increase, further

therapeutic uses may be found for this remarkablesubstance.

MITE versus MANSCABIES is still widespread. In a few districts

where its high incidence in 1942 provoked strenuousaction the epidemic peak may have been reached,but most clinics treated more cases during 1943 thanever before.

Diagnosis seems to present difficulties. Treatmentcentres find that at least a quarter of the cases sentin (apart from contacts referred as a precautionarymeasure) are not infested with the mite at all.In the past many genuine cases were first diagnosedas something else, but the present tendency, BACON 18thinks, is to diagnose it too readily, and the confusionis unfortunate because the more serious complaintwhich is present will probably be aggravated bytreatment for scabies. Moreover it is not nice,without due cause, to become " a potential candidatefor action under the Scabies Order (1941)." Theonly way of making quite sure is to find the acarus.The dermatologist with an initial flair and manyyears of experience may be entitled to diagnosescabies from the clinical picture. Finding the acarusis a trick which can be learned by almost anyone ina few hours. The first essential is a good light ;few even of the special clinics are so equipped.Otherwise only a lens and a needle are required,though some sort of microscope is useful (as in theMinistry of Health’s film- Scabies) to impress the

16. Sydenstricker, V. P., Singal, S. A., Briggs, A. P., De Vaughn,N. M. and Isbell, H. J. Amer. med. Ass. 1942, 118, 1199.

17. Marshall, W. J. Invest. Dermatol. 1939, 2, 205.18. Bacon, L. J. Med. Off. 1944, 71, 101.

patient with the " ferocity of the beast that is bitinghim." The technique for finding the acarus has beenwell described 19 and the whole process is manifest inthe film mentioned. Blind digging is seldom successful.The number of occupied burrows, even in a seriouscase, is likely to be small, perhaps only a dozen in all,but in the large majority of cases there are at leastone or two on the hands and wrists. Areas with

sepsis and impetigo should be avoided ; the mite onlylives in normal skin. Experience in Birminghamclinics has, satisfied BACON that identification ofthe acarus is not only practicable but essential for

efficiency, particularly in the recognition of relapsesand exclusion of reinfections. The irritation which

persists for a time after successful treatment is madeworse by the further application of sarcopticides.No-one should be misled by the fact that scabies as

seen today may seem to differ in appearance and symp-toms from scabies as it was seen before the war. The

interpretation of this observation is simple but import-ant. Before the war scabies was not very common andwas more familiar to doctors in touch with the poorestsection of the community. Most cases that camefor treatment were of long standing, with extensiveareas of secondary infection ; the number of parasitesand of burrows was small. Nowadays, when scabiesis common, it is often seen in the well-to-do and well-cared-for ; it may come under treatment, particularlyin contacts, within a week or two of infection. Insuch patients secondary sepsis is rare, and not beingsensitised they have little erythema and few obvioussigns of the disease. But to the initiated these

uncomplicated parasitic infections are not difficult todiagnose. Burrows can always be found, more

numerous indeed than in long-standing secondarilyinfected cases, though the absence of inflammationmakes them less apparent. Every case that istreated at this stage, before any serious disablement,will not only save that individual much discomfortbut, as this is the type of scabies most likely to betransmitted, it will help to keep the epidemic incheck. Although it is desirable for those diagnosingscabies to be able to find and remove the acarus it isnot necessary to do so in every case. The moreskilful one is in finding the acarus the less oftenwill it be necessary to perform the operation. Thebelief that scabies is a dirt disease still.persists. Yetwe now know that contact-especially intimatepersonal contact-between one cleanly person andanother suffering from scabies may result in trans-ference, and once the female mite has burrowed intothe skin (which she does within an hour) no amountof ordinary bathing or washing will dislodge her.The onset of clinical symptoms is then inevitable,though they may take a month to appear. Cleanli-ness is no protection against scabies.The best method of treatment is not yet agreed, but

on a survey of the various methods used the lowestcommon denominator-i.e., the simplest routinewhich produces satisfactory results-appears to bethat adopted by GRAHAM 20 who gives one painting onlywith the benzyl-benzoate emulsion recommended in theMinistry of Health circular of April, 1942, and agreeswith the circular of February, 1943, in not disinfestingclothes or bedding as a routine. His relapse rate isunder 1%. At the Poolsbrook centre attention is

19. e.g. Mellanby, K. Scabies, Oxford War Manuals, 1943.20. Graham, J. R. Brit. med. J. 1944, i, 130.