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conditions. General summaries of their observations,which were made in 1943-44, will be found in twopapers and in their recent book, The Biology ofHuman Starvation.2The subjects of the study were 32 conscientious

objectors who lived in the laboratory for a year. Fora control period of 3 months the men were given adiet supplying 3492 calories daily, and on this theymaintained their normal health and weight. Then for6 months the calorie value was reduced to 1570 daily,in the form of potatoes, cabbage, turnips, and cereals,with only a few grammes of animal protein per week-the kind of diet that people in northern Europeconsume in famines. On this they lost an average of24% of their body-weight and developed the classicalsigns and symptoms of famine victims. By the endof 6 months, however, through a remarkable series ofadjustments, most of the subjects were no longerlosing weight. Basal metabolism now accounted foronly 962 calories a day, compared with the initial1576 calories. Two-thirds of this fall was attributableto the reduced mass of their metabolising tissues andthe remaining third to less intense tissue metabolism.A more significant fall was in the calories used up intheir daily activities-from 1567 to 451 per day. Nochange was detected in the metabolic efficiency ofcarrying out such standard tasks as walking on atreadmill (after the necessary corrections for loss ofweight), so this last fall must be ascribed to voluntarycurtailment of physical activity. The men moved

slowly and cautiously, climbed stairs one at a time,and eliminated all unnecessary movements-meanswhich closely resemble those observed by LEYTON 3in prisoners-of-war. At the same time there were

profound personality changes. All the men became

apathetic, depressed, and introverted, avoiding socialcontacts so far as possible. Most of them were moreemotionally irritable than before, though their over-whelming physical lethargy usually prevented anyaggressive behaviour. Their aversion to intellectualeffort made them seem stupid, but psychological testsrevealed no impairment of memory, reasoning power,or verbal and arithmetical facility.

In the last 3 months of the experiment variousmethods of rehabilitation were compared. Recoverywas slow but ultimately complete. When they leftthe institute the volunteers were normal in most oftheir functions, but it was another 9 monthsbefore they regained full normality. They seemedto recover best on a good mixed diet of about 3500calories daily, with light exercise. Additional calories,protein supplements, and special vitamin preparationshad no apparent effect on the pace of recovery.Among the more detailed observations published

separately were some important ones on the tissuefluids 4 and the circulatory system.5 Nearly all thesubjects developed famine oedema. During semi-starvation the absolute plasma volume increased onlyslightly, and the total amount of extracellular fluid(thiocyanate space) was substantially unchanged. But1. Keys, A. J. Amer. med. Ass. 1948, 138, 500. Taylor, H. L.,

Keys, A. Science, 1950, 112, 215.2. Keys, A., Brozek, J., Henschel, A., Mickelsen, O., Taylor, H. L.

Biology of Human Starvation. Minneapolis: University ofMinnesota Press. London : Oxford University Press. 1950.Two vols. Pp. 1385. £6 10s.

3. Leyton, G. B. Lancet, 1946, ii, 73.4. Henschel, A., Mickelsen, O., Taylor, H. L., Keys, A. Amer. J.

Physiol. 1947, 150, 170.5. Keys, A., Henschel, A., Taylor, H. L. Ibid, p. 153.

owing to the great reduction in cellular mass there wasa relative increase in both extracellular fluid and

plasma volume. Throughout the experiment therewas a close correlation between the volumes, expressedin ml. per kg. body-weight, of plasma and of extra-vascular fluid. The observations support the viewthat famine oedema is a reflection of a simple dis-proportion between the losses of extracellular fluidand of cell mass following a defective supply ofcalories. In the present case oedema appeared withoutany reduction in plasma-proteins. The main cardiac

finding in the experiment was well-marked atrophyof the heart muscle, radiological measurements

indicating an average reduction of 17% in heartvolume ; a similar atrophy has been noted in necrop-sies of famine victims. The average pulse-rate becameprogressively slower for the first 8 weeks, when thebasic rate was 35 per minute, but thereafter it remainedabout the same. The bradycardia was not an indi-cation of heart-block. Electrocardiograms showedreduced voltages - of deflections but no importantchanges in rhythm. Both systolic and diastolic blood-pressures fell, and, in contrast with the pulse-rate,the pressures went on falling to the end of the experi-ment, the maximum reductions being 30 mm. Hg insystolic and slightly less in diastolic. These changeswere completely reversed on rehabilitation, and after32 weeks most of the cardiovascular measurementswere normal. Cardiac function, on the other hand,recovered more slowly, which confirms the empiricalfinding that famine victims need long and carefulconvalescence. All the volunteers became slightlyanaemic, with an average fall in haemoglobin level from15-1 to 11-7 g. per 100 ml. in 24 weeks. The causes ofthis anaemia are uncertain ; but it is agreed thatsevere anaemia in famine victims is not simply aconsequence of lack of calories or animal protein, soa search must be made for infections or other factors

adversely affecting the bone-marrow.The results of this experiment-skilfully conceived

and faultlessly executed-will be of great practicalvalue to administrators planning relief measures aswell as to doctors working in future famines. Andunless means are quickly found to increase the world’sfood-supplies and distribute them more equitably,6periodic famines seem to be an inescapable prospect.

Cell Embolism and MetastasisTHE pathways and propulsion of cells in and out

of blood and lymphatic channels remain subjectsfor fresh inquiry, though they are as old as cellularpathology itself. It appears from the work of MiLESand NIVEN 7 that the passage of polymorphonuclearleucocytes outwards through capillary walls is notdue simply to their motility and to physical changesof the endothelium in inflammation : for such passageto take place the intravascular pressure must probablyexceed that in shock, where leucocytes are not foundoutside’ capillaries in infected foci. Likewise the

entry of fixed cells into blood and lymphatic capillariesrequires both a breach in the vessel wall and a forcethat detaches the cells and drives them in. Thetrauma of bone fractures or blast will make a breachfor fat emboli ; but such trauma does not accountfor the emulsification or entry ’of the fat. Withregard to tumour cells, there is a tacit assumption

6. Leading article, Lancet, 1950, ii, 446.7. Miles, A. A., Niven, J. S. F. Brit. J. exp. Path. 1950, 31, 73.

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that their entry is effected by an invasive propertyinherent in the cells themselves ; and colour is lentto this hypothesis by the identification of hyaluroni-dase in some mammalian tumours and one fowl

tumour,8 and of collagenase in many.9 It remainsto be seen, however, whether one or both of theseenzymes are always produced by invasive growths,and whether they are always absent from benigngrowths. Secretion of enzymes of the mucinaseclass might account for extravascular infiltration ofcollagen and other connective tissues, as well as forbreaches in vessel walls ; and the possibility thatthese enzymes are present in actively invasivetumours cannot be lightly dismissed.Whether enzymes destructive of connective tissue

exist in tumours or not, there can be little doubt thatruptures and defects in vessel walls aid the entry of alltypes of embolic cell. By means of models, YOUNGand GRIFFITH 10 have studied the physical conditionsthat allow entry by cells lacking invasive power.Their model presupposed that capillaries (representedby a thin-walled collapsible tube filled with circulatingfluid) lie freely in a fluid medium (represented by abox reservoir containing the same fluid and poly-styrene beads to mimic cells). Beads passed throughholes into the tube only when the external pressureexceeded the pressure within the tube. In this

experiment an unstable equilibrium existed for a time,during which the terminal segment of the tubeoscillated, alternately closing and opening as theinternal pressure fell below and rose above the external

pressure. In living tissues, however, intersticesbetween fibrils of connective tissue are normallyfilled, not with fluid, but with a jelly-like substancewhich liquefies locally in inflammation and oedema;and YOUNG and GRIFFITH went on to investigatewhat happens when the collapsible tube is surroundedby a continuous glycerin jelly. With increased

pressure in the tube the alkaline fluid containedin it was forced through a preformed hole into thejelly, which eventually broke up as the pressureincreased. When the pressure in the tube was againreduced below that in the gel (which was impregnatedwith phenolphthalein) masses of broken-up jellypassed into the tube. The model suffered from oneserious limitation, of which YOUNG and GRIFFITHare aware : the tube representing a capillary vesselwas not, in their own words, " braced and guyedby strands of reticulin and collagen." When extra-vascular pressure rises, these external attachmentsmake all the difference to the lumen of thin-walledvessels ; instead of closing, as RIBBERT supposed andthe model shows, the walls of the vessels are pulledapart by the fibrils. This opening mechanism wasfirst suggested by GASKELL," and its existence hasbeen confirmed by PuLLINGER and FLOREY.12 Thusthe conditions that co-exist in life-rise of extra-vascular pressure with patent blood and lymphcapillaries-are those shown by YOUNG and GRIFFITHto favour cell embolism.By measuring the pressure inside intratesticular

grafts of Brown-Pearce carcinomata and comparingit with the pressure in normal ungrafted testes of the8. Pirie, A. Ibid, 1942, 23, 277.9. Gersch, I., Catchpole, H. R. Amer. J. Anat. 1949, 85, 457.

10. Young, J. S., Griffith, M. D. J. Path. Bact. 1950, 62, 293.11. Gaskell, W. H. Arb. physiol. Inst. Leipzig, 1877, 11, 143.12. Pullinger, B. D., Florey, W. H. Brit. J. exp. Path. 1935. 16, 49.

same rabbits, YOUNG and his colleagues 13 haveestablished that the pressure in the tumour, measuredas tissue resistance to injected saline, rises duringthe healthy growth of grafts, whereas in a normaltestis the pressure remains remarkably constant ;and this implies that pressure in the tumour risesrelatively to intracapillary pressure, which is assumedto be the same in both testes. Only a breach in thevessel wall is then necessary for forced entry byembolic tumour cells. Holes or ruptures are obviouslymade by haemorrhages and by the defects often found insinusoidal vessels of rapidly growing tumours. YOUNGand his co-workers suggest that haemorrhages maybe due to a temporary rise in intravascular pres-sure, which causes the endothelial walls to burst

mechanically. It is more likely, however, that bloodleaks, or is forced, out of the growing tips of thecapillaries that form continuously in response to thestimulus of the ever-growing tumour, and thattumour cells enter these same tips as well as thedefectively lined sinusoids. Haemorrhages in theirvan are a feature of growing capillaries ; and theadded volume of blood increases tissue pressure andstretches open neighbouring lengths of vessel. Theseare widened also by products of inflammation-oedema fluid and plasma, and possibly fluid exudedfrom vessels made hyperaemic by X-irradiation.YOUNG and his associates draw attention to manyconditions likely to increase pressure inside tumours :further growth and rise of pressure as time passes ;aspiration biopsies and other factors causing hoomor-rhage ; local anaesthetics adding fluid under tensionand palpation entailing compression from without.Though none of these mechanisms can be confidently

blamed for any particular metastasis in man or

in animals-so capricious are the ways of tumourcells-nevertheless their capacity for harm warns us toavoid them.

Danger in the Home. ON Dec. 14 the Radio Times published a sketchto illustrate the Postmaster-General’s annual injunc-tion to " post early for Christmas." It representeda little girl in a nightdress leaning across an unguardedopen fire towards a Christmas stocking hanging fromthe mantelpiece. An innocent, sentimental drawing ;yet hundreds of little girls in this country are burnedevery year, many of them fatally, in doing just thiskind of thing. A document recently issued by theMinistry of Works 14 shows that in 51 out of 306accidents to children which were studied in detailthe cause was lack of a fire-guard, and in a further14 the fire-guard provided was either too wide in themesh or so flimsy that any child could knock it over.Of nearly 7000 fatal accidents in the homes of Englandand Wales every year, about a fifth are due to burns andscalds ; and of course children are the chief victims.The report is issued for the benefit of research-

workers and " not for general publication " ; butits findings should have headlines in every popularnewspaper. The sources of information cover a widearea, and their volume should in itself lend weightto the results of the investigation. For fatal accidentsthe figures supplied by the Registrar-General and the13. Young, J. S., Lumsden, C. E., Stalker, A. L. J. Path. Bact.

1950, 62, 313.14. Ministry of Works, Chief Scientific Adviser’s Division : An

Inquiry into Accidents in the Home.