86

1. Lobund Reports, no. 3. University of Notre Dame, Notre Dame,Indiana. 1960. Pp. 182. 5$.

ciency. This is an interesting approach; but is it tenable ?Cerebral function is not unitary in the sense that cardiacor (within limits) renal or hepatic function is unitary.Some cerebral structures may function while others arein abeyance, with diverse effects on mentation. Even

biochemically (as Engel and Romano themselves observe),different parts of the brain may require different milieuxfor efficient functioning. While it is true that the electro-encephalogram rhythms slow characteristically in delirium,it is also true that such slowing may have a variety ofclinical causes. The important differential diagnosisis not between delirium and conditions such as depression,hysteria, or unusual forms of schizophrenia, which mayoccasionally present in a similar way, but between thevarying causes of delirium itself. The need is to analyserather than unify this symptom-or perhaps congeries ofsymptoms.

GERM-FREE ANIMALS

THE gallant at the court of Charles II might spend hisafternoon at his choice in writing verse or playing theviol or in " some chymical experiments ". Most ofDarwin’s work was done with eyes and fingers in hisstudy or the greenhouse at Downe. Today-althoughthe chief tool of research is still the forebrain-the

opportunities for scientific investigation are more andmore limited by the complexities of method and apparatus.In this respect the study of the germ-free animal is almostas difficult and expensive as atomic physics. It demandspremises designed for the purpose, equipment whichcannot be improvised from the store-room, and a largeteam of devoted workers with no other call on their time.So it is that there are not more than half a dozen instituteswhere this subject is pursued; but the slow advance inknowledge has at least the advantage that we can absorbit deliberately and thoughtfully.The third volume of the Lobund Reports from the

University of Notre Dame is therefore a welcome event.1The greater part is devoted to the germ-free chicken.In general the germ-free and conventional birds showno difference in weight for age and in rate of growth.Those organs which in the conventional bird are in closecontact with bacteria (e.g., the intestines and theirassociated lymph-glands) are smaller in the germ-freebird, which also has fewer circulating lymphocytes.There are minor differences in the aminoacid content ofthe bowel. The germ-free bird produces no antibodiesto the intestinal bacteria found in the conventional bird,unless autoclaved cultures of these are fed to it for someweeks. Similarly it produces antibodies to the bacteriawhich are abundant in its autoclaved diet. As judged bythese and other immune reactions, it is as capable offorming antibodies as the conventional bird. Fed on a" complete " synthetic diet, it shows no obvious signs ofvitamin deficiency. These findings are not unlike thosealready reported in germ-free mammals; but the manytedious experiments are a necessary prologue to anyfurther work, and this no doubt is already in hand. Amore original study is on the presence of protozoa andhelminths in germ-free rats, mice, guineapigs, chickens:and dogs. There are none-except in the dogs, and it haslong been known that puppies could be infected bymaternal nematodes in utero. A tribute to R. W. Glaseiis well deserved: it was he who first raised protozoa and

1. Wilson, R. H., Meador, R. S., Jay, B. E., Higgins, E. New Engl. J. Med.1960, 262, 956.

2. Darling, R. C., Cournand, A., Richards, D. W., Jr. J. clin. Invest. 1940,19, 609.

3. Blackburn, H., Brožek, J., Taylor, H. L. Ann. intern. Med. 1959, 51, 68.4. Turley, F. C., Harrison, T. R. Amer. J. med. Sci. 1932, 183, 702.

insects free from bacteria, and, as with many pioneers,the value of his work was not well recognised until afterhis untimely death.To the practising doctor the most rewarding aspect of

the study of the germ-free animal will probably be themechanism of bacterial infection. Nobody believes anylonger that infection is of the nature of a chemical

equation: host-f-parasite=disease. Here and there we aregetting hints which make it clear that the process is

something far more complicated. The germ-free animalhas already played a part in this newer knowledge, andwe can expect even more to come now that the spadeworkhas been done by the teams at Notre Dame and elsewhere.If there is a danger, it is as much semantic as patho-logical. Is a germ-free rat a rat at all ? That picturesqueand painful jellyfish the Portuguese man-of-war is thoughtto be a symbiosis of four or five distinct organisms: oneswims, another catches, another digests, and so on. Itcould be argued that the rat is not dissimilar in a state ofNature: one organism to move and fight and breed, anda million others to make the vitamins and protect theskin and mucous membranes against infection. Is it arat or a symbiosis ?

CIGARETTE-SMOKING AND PULMONARY

FUNCTION

IN sporting circles it has long been held that cigarette-smoking impairs lung function, and this belief has beenscientifically endorsed by Wilson and his colleagues 1These workers compared the results of lung-functionstudies in 14 persons who had never smoked with thosein 14 persons who had smoked at least 20 cigarettes a dayfor a mean period of 18 years. Preliminary screeningexcluded from the investigation anyone with symptomsor signs of respiratory disease or with an index of pul-monary mixing greater than 2-5% (the upper limit ofnormal according to Darling et al.2); and each smokerwas paired with a non-smoker of like body-surface,height, age, and environmental background.

In the smokers, as compared with the non-smokers,there was a significant decrease in the one-second forcedexpiratory volume, total lung capacity, maximum breath-ing capacity, total lung diffusing capacity, and meanmembrane diffusing capacity, and a significant increasein the index of pulmonary mixing and in the ratio ofresidual volume to total lung capacity. The pulmonarycapillary blood-volume in the two groups was similar, andthe carbon-monoxide concentration in the blood ofsmokers was not high enough to affect diffusion tests.These results confirm the observation by Blackburn

et al.3 that cigarette-smoking eventually depresses pul-monary function, and Wilson et al. suggest that theconflicting findings of Turley and Harrison 4 may beexplained by, among other things, the fact that theseworkers investigated students with only short smokinghistories. Wilson et al. warn us that in evaluating theresults of pulmonary function tests in the individualpatient the smoking history should be taken into account,and they suggest that " normal " standards of pulmonaryfunction established by studies in which the subjectstested included cigarette-smokers may have to be revised.