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levels of non-protein-bound cortisol in normal

pregnancy of 34-38 weeks’ duration with those in

pre-eclampsia. The results are analogous to the

Glasgow work on aldosterone, showing evidence ofsuppression. The unbound-cortisol levels at 9 A.M.,although lower, were not significantly differentfrom those in normal pregnancy. But the depres-sion of unbound cortisol at midnight was highlysignificant in the pre-eclamptic group. Urinary-free cortisol was also lower in the pre-eclampticwomen.

It is not entirely surprising that excess productionof cortisol or aldosterone cannot be invoked in thecausation of pre-eclampsia. As the Hammersmithworkers note, this condition can occur after adrenal-

ectomy or in Addison’s disease, and corticosteroidproduction from sources other than the maternaladrenals in pregnancy appears to be negligible.There is now little doubt that both cortisol andaldosterone are, in fact, suppressed in pre-eclampsia.The influence of the renin/angiotensin system onaldosterone is apparently a good deal less close inpregnancy than in other situations, such as sodiumdepletion and renal hypertension 14-the Glasgowgroup did not observe a significant correlation ofplasma aldosterone with renin or angiotensin II. Thecause of the depression of these various hormones inpre-eclampsia remains to be determined. Renin-substrate and non-protein-bound cortisol are both

capable of being stimulated by cestrogens 32,45 and thelower levels in pre-eclampsia could be a reflection ofplacental dysfunction. But other factors have to beinvoked to explain the suppression of renin and

angiotensin. While the aetiology of pre-eclampsiaremains a mystery, a pattern of biochemical dis-turbance seems at last to be emerging which suggeststhe possibility of an increase in the circulating levelof an unidentified pressor agent. There is much

scope for further work on the problem.

A.I.D.

THE decline in the number of children availablefor adoption has worsened the plight of infertilecouples who want children. Sometimes, where themale is azoospermic, or where maternal rhesus anti-bodies preclude safe pregnancy, an alternative methodof acquiring a child is sought. One of them is artificialinsemination by a donor other than the husband

(A.I.D.); and requests for A.I.D. are increasing. Thelast substantial British report, thirteen years ago,46condemned A.I.D. and saw no need to change the lawwhereby a resultant child is deemed illegitimate.Much of the debate which followed centred on ques-

45. Burke, C. W. J. clin. Path. 1970, 23, suppl. 3, p. 11.46. Report of the Departmental Committee on Human Artificial

Insemination. Cmnd. 1105. H.M. Stationery Office, 1960.

tions of the sanctity of marriage-whether it wasbroken by a wife who received the seed of a manother than her husband, or whether such an act,without concupiscence, could be innocent. Todaymany would still be worried by an apparent threat tofidelity in marriage; but public attitudes have changedso notably since 1960 that the time seems right for areappraisal of A.I.D. Could not the definition of

legitimacy now be extended to include a child bornas a result of A.I.D. ? And, for purposes of registra-tion, could not the husband be regarded as the child’sfather ? A panel appointed by the B.M.A., reportingin the British Medical Journal this week, reasonablythinks the answer to both questions is yes.The likely demand for donor insemination, were

the facilities to be made more widely available,should not be overestimated. Thorough investigationwould probably reveal relatively few couples whocould be helped. It has been calculated, on thebasis of estimates of donor insemination in Holland,that of approximately 470,000 marriages contractedannually in the United Kingdom, A.I.D. would be apossible treatment in no more than 1400 partner-ships at one time. The law, too, presents difficulties.It seems uncertain, for example, how it might viewthe transmission of diseases carried by the donor’ssperm, or the birth of a congenitally abnormal baby.A.I.D. does not safeguard patients from the conse-quences of normal sexual intercourse, but presumablylawyers would view unfavourably any failure bymembers of the medical profession to utilise existingtests whereby abnormal spermatozoa may be recog-nised. The question of injuries to unborn childrenis not yet resolved,47 and it may still transpire that achild is entitled to recover damages for an injurysustained before birth if it is caused by the negli-gence of another.

While much of the medical profession awaits theoutcome of legal discussions, it must be acknowledgedthat there is a small nucleus of doctors who nowundertake donor insemination in carefully selectedcouples. That they perform a valuable service, theB.M.A. panel agrees. In addition, other practitionershave expressed willingness to undertake A.I.D. on

suitable patients. If, however, this relatively simpleprocedure is to be done more often and by morepractitioners in Britain, it would seem wise to

establish referral centres, within the National Health

Service, having facilities for donor selection and forstudy of semen storage, and where confidential

long-term follow-up records may be maintained.This is another of the panel’s recommendations.There is need for information not only on the

genetic effects of A.I.D. but also on its impact onpersonal relationships in families. The medical

profession cannot, at the moment, ignore the legalquestions; but it needs to concern itself particularly47. See Lancet, Jan. 27, 1973, p. 213.

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with questions such as these, and to ask itself howmedical and ethical standards may be safeguardedin relation to A.I.D.

THREE SCORE AND TEN AT THE FUND

IN view of the sheer topicality of cancer research,it is salutary if not surprising to be reminded that theImperial Cancer Research Fund (I.C.R.F.) has beenengaged in its pursuit for all of seventy years. Sincethe publication in The Times on April 18, 1902, ofits first appeals letter, the Fund has grown into a

large and professional research organisation that

spent, during its seventieth year, almost El,600,000on actual research and over E900,000 on new buildings.The body of the latest report consists of four essayson chosen aspects of cancer research. According toJ. Tooze, if viruses are involved in the genesis ofhuman cancers it is more likely that they are trans-mitted in the egg and sperm than that they are

transmitted from person to person in the same wayas agents which cause infectious disease. If this werenot so, he argues, one would have expected epidemiolo-gists to have encountered more evidence than theyhave of clustering in time and space of particulartypes of cancer. This is hardly a convincing argument,since it could be asserted with equal force that trans-mission by egg and sperm should be associated withmuch more evidence of a familial tendency in theoccurrence of cancer than is the case. A more plausibleview is that cancer is a rare consequence of the

presence of certain viruses, irrespective of how orwhen they enter the body, and a consequence that isdependent on the fulfilment of one or more otherconditions which affect the way in which viruses andthe cells they enter interact. Much current researchon the particular viruses associated with malignantdisease in mice, chickens, and other species may havelittle direct relevance to the study of human malignantdisease: both the viruses themselves and the con-ditions which have to be fulfilled if they are to giverise to cancer may be peculiar to those species or tothe laboratory. Nevertheless, elucidation of themechanisms might lead indirectly to a better under-standing of what can be done to prevent, detect, orattack malignant disease in man. For instance, it is

possible that one of the genes present in the polyomavirus codes for a protein which transforms normalcells into malignant cells. Identification of the geneand of the protein might lead to new ways of controllingcancer in man. Similarly, confirmation of the findingthat hamster cells transformed by simian virus 40release a chemical factor which stimulates cells to

migrate might, by improving understanding of whycancers invade and how they metastasise, also lead tobetter methods of cancer control.

Carefully planned systematic investigations of theresponse of human beings to anti-cancer treatmentshave led to considerable improvements in treatment.By combined treatment with cytosine arabinosideand daunorubicin it is now possible to obtain com-plete remissions in up to 60% of patients with acute

1. Seventieth Annual Report and Accounts of the Imperial CancerResearch Fund, Lincoln’s Inn Fields, London WC2.

myelogenous leuksemia. Furthermore, remissions soinduced can be effectively prolonged by immuno-therapy using a non-specific stimulus in the form ofB.C.G. vaccination together with specific immunisationwith irradiated human leukxmia cells. More generally,there are an increasing number of examples of situa-tions in which better results are obtained by inter-mittent therapy with high doses of chemotherapeuticagents than by more continuous therapy with thesame agents in lower dosage. Many drugs used in thetreatment of cancer damage immune mechanismsthat are themselves involved in the defence againstthe growth and spread of cancers. Intermittent

therapy allows repair of those defences.N. A. Mitchison lists reasons for feeling that

tumour immunology is about to fulfil its promise.The subject has at last outgrown its disreputablehistory, in the course of which tumour-specificantigens became badly confused with transplantationantigens and outrageous claims were made for serumtherapy and diagnosis. There is now unequivocalevidence of the presence of lymphocytes cytotoxic totumour cells in individuals bearing tumours, that

specific serum factors may block the activity of theselymphocytes, and that under certain circumstances itis possible to counteract these blocking factors. Inview of the discovery of antigens of two kinds (onco-fetal and virus-induced) that are common to a rangeof tumours, the prospects of preventing cancer byimmunisation are perhaps not quite so bleak as theyonce seemed. The results of a large-scale vaccinationtrial against Marek’s disease of poultry (a lympho-sarcoma-like disease caused by a D.N.A. virus) will beeagerly awaited. Much attention is being paid toimmunological methods in cancer detection, especiallyto carcinoembryonic antigen secreted by tumours ofthe colon and to alpha-fetoprotein secreted by hepa-tomas. These products, however, seem to be charac-teristics, not of tumour cells as such, but of particularkinds of cell in a proliferative or inflammatory phase.For this reason it looks as though false-positiveresults are not merely a feature that can be overcomeby improvement in methodology, but a basic drawbackof tests based on detection of these proteins in cancerscreening. In any case, there is little reason at presentto hope that tumours of other sites will be found torelease equally characteristic products. Perhaps a

more promising approach to the application of

immunological methods in cancer detection will beto examine the reaction of lymphocytes from apparentlynormal individuals with cells of a number of well-established human cancer cell-lines. Results of some

investigations of this kind have been encouraging.As with dress, there are both traditions and fashions

in research. The I.C.R.F. has traditionally beeninterested in immunological aspects of the relationbetween tumours and their hosts. Because of anincrease in general knowledge and vast improvementsin techniques, this area of research has now becomefashionable. The background of tradition combinedwith the intellectual strength of the team of scientistsnow assembled at the Fund under its director, DrM. G. P. Stoker, bid fair to contribute substantiallyto man’s understanding of cancer and to his chanceof controlling it.