402

that one of the deciding factors is the side on which thegonad is situated.

Fetal testes in rats 10 and mice 11 are markedly largerthan ovaries, and this leads to the question whether thelarger size is the cause or the result of testicular differentia-tion. The present data favour a causal relation. Indeed,if the development of testicular rather than ovarian tissuecan be affected by so feeble a force as lateral asymmetry,it would seem unlikely that the information normallyprovided by the Y chromosome is very specific. Fetaltestes are distinguished by their precocious growth anddifferentiation,12 in contrast to the slow developmentcharacteristic of the ovary. The early growth of the testisis normally ensured by the presence of a Y chromosome, 10while in hermaphrodites the likelihood of the fetal gonaddeveloping into a testis is increased by being situated onthe right side of the body.

I thank Dr Sylvia Lawler and the staff of the Fetal Tissue Bank,Royal Marsden Hospital, for supplying the fetal gonads, and MrGeorge Barrett for serial sectioning. This work was supportedby a grant from the Science Research Council.

Galton Laboratory,University College London,

Wolfson House,4 Stephenson Way,London NW1 2HE. URSULA MITTWOCH.

BETA-BLOCKADE AND HEART WEIGHTS

SIR,-The conclusions of Dr Vaughan Williams andDr Raine (Nov. 2, p. 1048) are very interesting. It is,however, regrettable that no blood-pressures and blood-pressure changes were reported, since chronic administra-tion of P-blockers may have had a hypotensive effect. Thisin turn could have been the cause for the lower ventricularweights of the treated rabbits, compared with the controls. 13It is still unclear, therefore, which is the egg and which isthe chicken.

Beilinson Hospital,Petah Tiqva,

Israel. YEHUDA M. TRAUB.

BLOOD AND URINARY NICOTINE INNON-SMOKERS

SIR,—I was pleased to see the article on nicotine levelsin non-smokers by Dr Russell and Mr Feyerabend (Jan.25, p. 179). They find that the urinary nicotine in non-smokers has a mean level of 12°4 16°9 ng. per ml. (standarddeviation) (table 11). That means that the 15% or so ofthe population who lie one standard deviation below themean must have negative quantities of nicotine in theurine. What do negative quantities of nicotine look like ?

Sadly, on looking at the individual values and the figureI see that it is nothing new. Only the usual mistake has beenmade. The authors clearly recognise in their figure thaturinary nicotine levels are logarithmically distributed, notnormally distributed on an arithmetic scale. Yet they usearithmetic statistics. The same mistake is constantlybeing made with serum-enzyme activity and many othermeasurements.

Biological measurements are more often logarithmicallythan arithmetically distributed. Statistics based on normaldistribution can be used if the log of the values is taken andtreated in the usual way. The anti-log of the mean is thenthe geometric mean and one standard deviation either sidecan be given in the log form or in its unsymmetrical arith-

10. Mittwoch, U. Genetics of Sex Differentiation. New York, 1973.11. Mittwoch, U., Buehr, M. L. Differentiation, 1973, 1, 219.12. Jost, A. in Schering Workship on Contraception: The Masculine

Gender (edited by G. Raspé), p. 3. Oxford, 1973.13. Hall, O., Hall, C. E., Ogden, E. Am. J. Physiol. 1953, 174, 175.

metic form. Statistical treatments that ignore this areerroneous and misleading. Unfortunately the conclusionsdrawn in the particular case of nicotine transfer to non-smokers do not depend on the statistical analysis andremain disturbingly valid.

University College HospitalMedical School,University Street,London WC1E 6JJ. A. E. M. MCLEAN.

EFFECT OF BORDETELLA PERTUSSISVACCINE ON GROWTH OF HEPATOMA

SIR,-Several adjuvants, such as B.C.G. and Coryne-bacterium parvum, inhibit tumour growth.1-5 Dependingupon the route of injection, Bordetella pertussis also inhibitstumour growth. 6,7 Although the mechanism remainsundefined, it functions as an immune potentiator. Thegrowth of well-established hepatoma 5123 tumours wasinhibited by either intravenous or subcutaneous injectionsof hepatoma cells and pertussis vaccine.’ 7 Conversely,growth was enhanced if the combined treatment was

administered before tumour transplantation. The effectsseemed to be tumour specific.’ 7 Moloney lymphomaisografts were facilitated in mice (strain C57L/KL) afterintraperitoneal injection of pertussis vaccine. 8 B. pertussisvaccine (P.v.) has been used for active immunotherapy inpatients with acute leukaemia.9 The results of these treat-ments suggest that this vaccine inhibits tumour growth.In an effort to determine the role of P.v. in tumour

inhibition, female Buffalo rats, weighing 230-260- g.,were inoculated with cells from Morris hepatoma 7777.Isografts of Morris hepatoma 7777 were obtained from

1. Zbar, B., Bernstein, I., Tanaka, T., Rapp, H. J. Science, 1970,170, 1217.

2. Zbar, B., Bernstein, I. W., Rapp, H. J. J. natn. Cancer Inst. 1971,46, 831.

3. Zbar, B. Natn. Cancer Inst. Monogr. 1972, 35, 341.4. Woodruff, M. F. A., Boak, J. L. Br. J. Cancer, 1966, 20, 245.5. Halpern, B. N., Biozzi, G., Stiffel, C., Mouton, D. Nature, 1966,

212, 853.6. Likhite, V. V. Cancer Res. 1974, 34, 1027.7. Wissler, R. W., Craft, K., Kesden, D., Polisky, B., Dzoga, K.

Proc. First Congr. Transplant Soc. 1968, p. 539.8. Floersheim, G. L. Nature, 1967, 216, 1235.9. Guyer, R. J., Crowther, D. Br. med. J. 1969, iv, 406.

Fig. 1-Effect of P.V. on growth of hepatomas.All rats received transplantable Morris hepatoma 7777 sub-

cutaneously.