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clear. Studies of electrolytes have a place in long-continued coma.

The treatment of the severe head injury is clearlybecoming less the province of the inactive master thanit has been hitherto.

1. Kalabukhov, N. I. in Recent Research in Freezing and Drying (editedby A. S. Parkes and A. U. Smith); p. 101. Oxford, 1960.

2. Cater, D. B., Weiss, L. Nature, Lond. 1959, 183, 1521.3. Smith, A. U. Biol. Rev. 1958, 33, 197.4. Giaja, J., Andjus, R. C. R. Acad. Sci., Paris, 1949, 229, 1170.5. Andjus, R. K., Lovelock, J. E. J. Physiol. 1955, 128, 541.6. Goldsveig, S. A., Smith, A. U. ibid. 1956, 132, 406.7. Gray, L. H. Brit. J. Radiol. 1957, 30, 403.

HYPOTHERMIA AND X-IRRADIATION

IN their response to cooling animals fall into three

groups: they may be homoeotherms, keeping a fairlyconstant body-temperature regardless of the environ-

ment ; they may be poikilotherms, their body-tempera-ture tending to follow that of the environment; or theymay exhibit each type of response at different times.

Thus, hibernating mammals may be regarded as poikilo-therms during the winter, and homoeotherms during thesummer. The newborn offsprings of many homoeothermspass through a poikilothermic stage lasting a few days,during which they can withstand transitory profoundhypothermia.The practical importance of this classification is that

when homceotherms are cooled to body-temperatures ofbelow about 15°C, their spontaneous respiratory andcardiac movements cease and they cannot be revivedsimply by warming. On the other hand, poikilothermsmay be cooled to temperatures around 0°C and be moreor less restored to their former state by rewarming.In poikilotherms, at body-temperatures below about 15°C,circulation and respiration continue at much lower rates.For instance, the number of heart-beats per minute in thehibernating bat (Nyctalus leisleri) at 4.1 oe is 16, comparedwith 420 in the active animal at 37.3OC.l Although themetabolism in hibernating mammals is at a low level theirrequirements are also low, and the compensatory physio-logical mechanisms are such that they are adequatelyoxygenated. In contrast, when homreotherms and theirnewborn are cooled to below 15°C, circulatory and

respiratory movements cease completely, but as theanimals still have some metabolic requirements theytend to become profoundly hypoxia. 2 The resistance ofanimals to cooling has been ably reviewed by Smith.3Studies on the effects of various agents on cold mammalshave until quite lately been limited to hibernators andnewborn animals below 15°C, and to homoeotherms above15°C. This was because it was technically impossible toresuscitate homoeotherms which had been cooled to, andmaintained at, temperatures much below 15°C. In 1949

Giaja and Andjus described how rats cooled to 1°C intwo stages could be reanimated by applying a hot spatulato the precordium and insufflating the lungs. Onlyabout 25% of the rats were resuscitated by this technique,and few of these survived longer than several days. Later,Andjus and Lovelock 5 and Goldsveig and Smith 6

developed less traumatic methods for resuscitating small,ice-cold mammals, some 80% of which survived.Much radiobiological work has shown that the sensi-

tivity of cells and tissues to X-irradiation is considerablymodified by the amount of oxygen in them. 7 Well-oxygenated tissues are approximately three times as

sensitive to ionising radiations as anoxic tissues. The

modifying effects of cold on X-irradiated animals hasbeen reviewed by Weiss. 8 Doull and Dubois 9 studiedthe effects of X-irradiation on hibernating groundsquirrels (Citellus tridecemlineatus). This work, incommon with other studies on hibernating mammals,showed that the appearance of irradiation damage is

greatly delayed, but that it appears in full when theanimals are warmed to be the " active state " and noultimate protection is afforded by hibernation. Osbornand Kimeldorf 10 found that hibernation induced after

exposure to radiation also delayed the onset of damage,but again provided no ultimate protection. In terms oftissue oxygenation, these findings were to be expected. In1941 Evans et al.11 demonstrated a distinct increase in theradioresistance of the skin of newborn rats irradiated at0-6°C. In 1956 Hornsey 12 reported that no mice of theT strain survived longer than 30 days when subjected to900r of whole-body X-irradiation at normal body-temperatures ; but mice irradiated with the same doseat body-temperatures of 1°C, and subsequently resusci-tated, all survived. On this and other data, a protectivefactor of 2.8 was associated with hypothermia of 1°C.This factor is what would be expected if hypothermicradioprotection is in fact due to the associated profoundhypoxia. Weiss has carried out detailed work on miceirradiated at body-temperatures of 1°C on the protectionafforded to the testes,13 the spleen, 14 and the hxmopoietictissues 15 and on fertility in the female. 8 In all instances

hypothermia during irradiation, but not after it, was asso-ciated with considerable radioprotection. Work on cell-cultures, 16 where hypoxia and hypothermia could be studiedindependently, suggested that the radioprotection exhibitedby hypothermic mammals at 1°C is at least largely due toconcomitant profound hypoxia. The results of the workdone on the radiosensitivity of mammals at 15°C, whilethey are still breathing and have a functioning circulatorysystem, is conflicting. After reviewing the evidence, Weiss 8concludes that the true protection afforded to mammalsirradiated at 15°C is slight compared to the protectionobtained at 1°C, and is not readily explicable in terms ofthe " oxygen-effect ".The techniques of induction of profound hypothermia

in the man and the subsequent resuscitation are muchmore complex than the corresponding techniques insmall animals. Nevertheless the experimental work has abearing on two important clinical possibilities. The firstconcerns the treatment of disseminated malignantdisease by whole-body irradiation. The presence withinthe tumour bed of highly radioresistant anoxic foci is

thought to be an important factor limiting the effective-ness of radiotherapy. 7 Wright and Howard-Flanders 17suggested that, if patients were made " anoxic " duringirradiation, they could withstand a higher dose of X-rays,whereas the sensitivity of the anoxic foci would remainunaltered. Weiss 8 14 18 has suggested that this could beaccomplished in practice by irradiating hypothermicpatients who could safely be made profoundly hypoxic,8. Weiss, L. Brit. med. Bull. 1961, 17, 70.9. Doull, J., Dubois, K. P. Proc. Soc. exp. Biol., N.Y. 1953, 84, 367.

10. Osborn, G. K., Kimeldorf, D. J. J. exp. Zool. 1957, 134, 159.11. Evans, T. C., Goodrich, J. P., Slaughter, J. C. Proc. Soc. exp. Biol., N.Y.

1941, 47, 434.12. Hornsey, S. Nature, Lond. 1956, 178, 87.13. Weiss, L. J. Endocrin. 1959, 19, 22.14. Weiss, L. Brit. J. Radiol. 1960, 33, 32.15. Weiss, L. Int. J. Rad. Biol. 1960, 2, 409.16. Weiss, L. ibid. p. 20.17. Wright, E. A., Howard-Flanders, P. Acta radiol., Stockh. 1957,

48, 26.18. Weiss, L. Proceedings of the Tenth International Congress on Refrigera-

tion; vol. 1, p. 628. London, 1960.

386

since their hypothermia would protect them from thedangers of hypoxia without materially altering the radio-sensitivity of their tumours. Secondly, in people exposedto ionising irradiations the ill-effects could perhaps bedelayed by hypothermia, while bone-marrow infusionsor other therapy were being organised.

THE METRIC SYSTEM IN PRACTICE

SLOWLY we are feeling our way towards full applicationof the metric system. The ultimate replacement of theapothecaries’ by the metric system for all pharmaceuticalpurposes is likely to lead to the adoption of this system formeasuring inches, feet, and yards; for length and volumeshould be as inseparable in our minds as part and parcel,and how can this be so without the same language ofmeasurement ?

Yet the adoption of the metric system even in pharma-cology (which will become all but obligatory in 1963 whenthe British Pharmacopaeia will contain no other notation)is not devoid of difficulties. Two years ago one of our

university hospitals-the United Birmingham group-decided to anticipate the British Pharmacopaeia in thisrespect. The immediate problem for the standing pharma-ceutical committee was to equate the metric with the

imperial dosage system and to explain this conversion tostaff at all levels. For convenience close approximationswere adopted. Thus gr. 1/4, so familiar for morphine,became 15 mg.; and gr. 3, familiar for certain barbiturates,became 200 mg. Conversion tables for solids and fluidswere printed on two sides of a small indestructible cardconvenient in size for both the uniform frock and thewaistcoat pocket. No prescription was to be accepted bythe hospital pharmacies unless it was set out in the metricsystem. The changeover was achieved without oppositionor complaints-though to those of middle age it is not

always easy to think of a dose of morphine as 15 mg., eventhough 1 g. of sulphonamide causes no difficulty : we havebecome accustomed to our anomalies. The hospital staffhad to decide whether letters to general practitionersshould continue to be written in the imperial manner.Most decided to discard this here too; for to do otherwisewould be to connive at the dual system that they wereattempting to end and would destroy the faith of newgraduates.One consequence has been wholly advantageous: wards

are now being equipped with metric measuring-flasks andutensils, thus eliminating an arrangement that was both asource of error and an unwarranted burden on the nursingstaff, who previously had had to measure in ounces andpints and convert (without the aid of tables) to millilitresand litres in order to satisfy the demands of an up-to-dateconsultant. But habit dies hard: at least to one ward sisterthe bottle of intravenous fluid had always been and stillwas a pint bottle-why not, since so many around her stillspoke of giving a patient x pints of saline ? She thereforerecorded each bottle as 600 ml., not appreciating that eachnow contained 500 ml.

Unification requires that we shall speak and write interms of centimetres. This is perhaps rather more diffi-cult : " the last 50 cm. of the small intestine " has a strangering. Moreover it is hard enough to persuade a medicalstudent to procure any tape measure (the stethoscope,though far more expensive, is bought readily enoughbecause it is a status symbol); and tape measures gradedin centimetres, though made, are hard to come by.

CURRENT MEDICAL RESEARCH

WHILE he was demonstrating a particularly abstractinvention Edison was asked what possible value it couldhave. He countered, we are told, with the question:" What is the value of a newborn baby ? " The value ofmany of the projects sponsored by the Medical ResearchCouncil is apparent immediately; that of others (as withEdison’s baby) less immediately.Work on interferon comes into the first category; for

this substance, found in tissue-cultures after incubationwith an inactivated virus, inhibits, in wide-spectrumfashion, the growth of many other viruses. Earlyenthusiasm about the therapeutic value of such an agentwas tempered by the possibility that it might proveintrinsically toxic, antigenic, or much less effective in vivothan in vitro. These possibilities have now been investi.gated, with results which indicate that interferon mayhave important clinical applications.An examination of the plasma-kinins seems to belong

to the second group; for the function of these compounds,even in normal physiological processes, is still obscure.They are polypeptides formed from plasma by the actionof proteolytic enzymes such as trypsin. In contact withexposed nerve-endings they give rise to severe pain, andwhen injected intravenously cause a fall of blood-pressureby relaxing the peripheral vessels. They may possibly beresponsible for reactive hyperaemia, and for the increasedblood-supply to skeletal muscle during exercise. Moredefinite grounds exist for believing that they play a partin the vascular changes which persist for so long inburned skin. The kinins are widely distributed: the urine,sweat, and saliva of many animals have been shown tocontain them, and their presence in wasp-venom m-

doubtedly accounts for much of the pain and swellingresulting from a sting.The drivers of London’s double-decker omnibuses

have been found to be some three times more liable tosudden death from heart-failure than the conductors,Further work has been directed towards examining thehypothesis that such a difference was due to the two jobsattracting contrasting somatotypes. Age for age, driversare larger round the chest than conductors; but study ofother occupations suggests that the death-rate fromischaemic heart-disease is commonly higher amongsedentary workers. Radio and telegraph operatorshave a particularly high mortality, postmen a muchlower one.

Twelve such items in its programme are described atlength in the report of the Council to Parliament,Formerly this intriguing resume of current researchproblems was available only to those who purchased thefull report, the greater part of which was concernedwith administrative matters. Now, however, the articles I

dealing with these projects are published separatelyat a modest price. These accounts are so topical in nature,and so catholic in appeal, that they are certain to be widelyread.

l

The title of Dr. EDITH SUMMERSKILL has been gazetted as

BARONESS SUMMERSKILL, of Ken Wood, in the County of, London.

1. Current Medical Research: a reprint of the articles in the report of theMedical Research Council for 1958-59. H.M. Stationery Office, 1960.3s. 6d.