THE LANCET, JANUARY 2, 1971

If the circulating antibody was the product of donor cells, this differential cytotoxicity would be expected. There is also the possibility, however, that the recipient's lymphoid tissue had not been replaced by donor cells but that the pat ient ' s skin cells carried an alloantigen not present oh his ' lymphoid cells. BoYsE et al. x~ demonstrated ~n mice the existence of alloantigens with this tissue-'limited distribution. If such antigens do also exist in man, they could present another class of antigen potentially capable of inducing a t issue-limited form of G.v.~L reaction.

At present the scope for ~linical bone-marrow transplantation is obviously small. But iCe i the r specific tolerance or immunolpgical enhancement become clinical possibilities, the prospects "could change radically.

TESTING NEW DRUGS EARLY testing of new drugs in man is of the utmost

,concern both to doctors and to the pharmaceutical industry. For the doctor, it may mean the prompt detection of a treatment superior either in efficacy or lack of toxicity to any hitherto available. For the industry, the early selection of a promising drug , or the recognition of unwanted and unacceptable side- effects, would be a great ecor/omic asset, promoting the more efficient use of research and development resources. Furthermore, with the advent of the Medicines Commission, the requirements for t e s t i n g of drugs, once voluntary, become mandatory. I t is vital, therefore, that means should be readily accessible for the study of new drugs in normal subjects and in patients.

Implicit in a report 15 by a working-party of the Medico-Pharmaceutical Forum, 1° which has been studying the organisation of early clinical studies of new medicines in the United Kingdoms is the belief that the place for such studies, or the centre of their organisation, should be units of clinical pharmacology.

. - " J f ' o

Such a umt should be part of each medical school and also a feature of certain other suitable centres, making a total of 25-30 units in Great Britain. Most units Would cover a range of drugs and diseases, although individual members of a unit would tend to speciakise in some particular area. The minimum cost of setting

up a workable unit with 2 established staff, a research fellow, technical and secretarial assistance, running costs, and capital equipment would be about £40,000 in the first year, and £20,000 in subsequent years. This money should come from Government sources-- namely, the Department of Health and Social Security and the Department of Education and Science." Additional support by funds from industrial firms for

i4 . Boyse, E. A., Lance, E. M., Carsweli, E. A., Cooper, S., Old, L. ]'. Natu~'e~ 1970~ 227, 901.

15. Medico-Pharmaceutical Forum: a report by the Forum's committee on clinical pharmacology on facilities for the early clinical studies of new medicines. 1 Wimpole Street, London W1M 8AE. October, 1970.

16. The Forum was established in 1968, under the chairmanship of Prof. D. R. Lat~rence, to provide an opportunity for representatives of established medical institutions, on the one hand, and of the pharmaceutical industry, on the other, to discuss problems of mutual interest.

work oriented to'yards their projects o r products would enable the units to expand and increase their work output. When work is done for industry, agree- ments with the company concerned should be negoti- ated after the project has been costed on a realistic basis, taking into account the time spent by scientific staff and technicians, use of materials, and deprecia- tion of instruments.

There are two aspects of the subject on which the report does not dwell and to which the Forum might profitably give attention. The first is the training of clinical pharmacologists. The report suggests that at least 5 new units should be set up in the next academic quinquenulum, plus the development of existing nucIei in medical schools with a lecturer in clinical pharmacology but little or no supporting facilities. If, however, the report is right in estimating that there are less than 10 units at present in existence in the United Kingdom, and that most of them are small, then it is imperative that urgent consideration be given to the training of clinical pharmacologists to supervise the service, teaching, and research activities of the proposed new departments. This matter has recently been discussed in a W.H.O. technical reportW The second aspect is the role of the whole-time medical adviser in the pharmaceutical industry. The Associa- tion of Medical Advisers in the Pharmaceutical In- dustry has already concerned itself, through symposia

-and publications, with p'roblems Of clinical assessment of new drugs, and close association between medical advisers and clinical pharmacology units is essential. Such links can be nothing but beneficial to both parties. The inauguration of a section of clinical pharmacology of the British Pharmacological Society 18 has provided an opportunity for all those concerned in the study of drugs in man to meet and discuss their work. I t is to be hoped that this exchange of ideas between medical scientists working in different areas of pharmacology, together with the establishment of clinical pharmacology units staffed by scientists and supervised by trained clinical" pharmacologists, will result in the more rapid recognition, testing, and use of promising drugs.

MERCURY IN FISH MERCURY levels ranging from 0.1 to 0.8 mg. per leg.

have been found in samples of canned tuna fish bought in central London on Dec. 16. Following the discovery of high mercury content in canned tuna in the United States, the Government Chemist has now examined over 50 samples from London and elsewhere. No-one is certain just how the mercury got there, though fungi- cides and industrial wastes are usually named as the original culprits. The details of the food chain which carries the mercury ~o the tuna are not dear ; but the contamination must be widespread, since mercury has been found in fish from many different seas. In Britain the Government has told housewives that there is no reason why they should not buy tuna fish, though in Sweden the advice to the public has been to eat fish no more than once a week. In London the Minister of

17. Tech. Rep. Set. Wld Hlth Org. 1970, no. 446. 18." Lancet, 1970~ i, 129.

28 THE LANCET, JANUARY 2, 197i

Agriculture, Fisheries, and Food is to follow his experts' recommendation and arrange for extensive monitoring of all possible sources of methyl mercury intake. The view is that no necessity exists to set a limit for the level of mercury residues in canned tuna fish, because it does not figure largely in the British diet. But the worry is that methyl mercury may be finding its way into other foods; and the Minister's advisers make it plain that they will want to reconsider their decision as the results of further analyses become available.

W H Y ONLY T W O C O R O N A R Y ARTERIES?

MANY must have looked at a human heart and wondered why there are three aortic cusps but only two coronary arteries. A third coronary artery arising from the "non-coronary" cusp is an extreme rarity, even in grossly malformed hearts. The embryologists can explain why the pattern is set, t but all the same, considering the importance of the coronary circulation, the tortuous course of the right and left coronary arteries and their branches, and the fact that they dispute predominance in the vulnerable area at the back of the heart, a third coronary artery might be a distinct advantage. Indeed, the term " th i rd coronary artery" has been applied to the conus artery arising from the right coronary cusp, 2 or to a large branch of the anterior descending branch of the left coronary artery. ~ So rare is a genuine third coronary artery arising from the non-coronary cusp that the name is thus pre-empted; and the possibility is dismissed in the classic work on comparative cardiology.;

But it seems that the mammalian pattern of right and left coronary arteries is not as fixed as had been assumed. In the white-tailed virginian deer (Odocoileus virginiensis borealis) in New York State, Bishop and her colleagues 5. ~ found a third coronary artery, arising from the non-coronary cusp and termed by them the "posterior coronary artery ", in 111 hearts of the 1106 deer hearts examined. The frequency in various herds ranged from 3"6% to .16"2%. 8 They have also seen one example in a caribou, e and this artery is now re- corded in 7 eland ( Taurotragus coryx), 7 4 kudu ( Trage- lophus strepsiceros), and 4 wildebeeste (Connoch~etus taurinus). I t has not, it seems, been seen in a variety of unspecified South African ~ and North American " mammals. In the deer this posterior coronary artery 6 passes directly backwards, giving branches to the sino- atrial node, the atrioventricular node, and the upper part of the septum, going on to supply the area of disputed coronary predominance. When the third artery is present, the calibre of the other coronary arteries, notably the left circumflex, is correspondingly reduced.

1. Goldsmith, J. B., Butler, H. W. Am. ] . Anat. 1937, 60, 105. 2. Schlesinger, M. ] . , Zoll, P. M., Wessler, W. Am. Heart J. 1949,

38, 823. 3. Brink, A. I. Clin. Proc. 1949, 8, 137. 4. Robb, I. S. Comparative Basic Cardiology. New York, 1965. 5. Bishop, M. B., Free, S. L., Davies, 1. N. P., Albert, R. P. Fedn Prac.

1968, 27, 357. 6. Bishop, M. B., Free, S. L., Davies, J. N. P., Albert, R. P. Am. Heam

J . 1970, 80, 785. 7. Basson, P. A., McCully, R. M..71 S. Aft . vet. me& Re$. 1969, 40,102.

Clearly, the coronary-artery pattern is not as set at had been believed, and a new look should be taken at the aortic root and the development of the coronar~ arteries. Other animals should be examined to de. termine how wide is the distribution of this third artery. The large numbers of wild animals killed i~ control operations could provide the means for su~ inquiries.

T R E A T M E N T OF CANCER OF THE COLON

IN 1953, .Turnbul l and his associates t,s at the Cleveland Clinic adopted a " no-touch isolation~ technique for the treatment of colonic cancer. They did so because of the observation that handling of tumours may disseminate malignant cells and promote metastases. 3 This course was supported by the finding of malignant ceils in the portal venous blood of patients with colonic carcinoma. ~,s Unneces. sary preoperative palpation of the turnout was avoided and at operation the skin was prepared by lavage rather than scrubbing. Resectability of a tumour was assessed early in the operation by looking for duo. denal or pancreatic infiltration. The tumour area itself was not handled until after ligation and division of the lymphovascular pedicles and transection of the colon.

Turnbul l " has analysed the outcome in 676 consecutive patients with adenocarcinoma o f the colon treated by this technique between 1950 and 1964. There was an impressively low operative mor- tality of 2-2%. ~-9 Age-corrected or actuarial sur. rival-rates were recorded and these give higher figures than the more commonly used crude survival-, rates. Most of the turnouts were histologically moderately undifferentiated, and a clinicopathological classification into stages A, B, C, and D was used. The overall age-corrected survival-rate at five years was 61%, compared with between 35% and 55% in other centres. ~° 30% of Turnbul l ' s patients were in stage D (metastases, peritoneal seeding, parietal or adjacent organ invasion), and of these only half had resectable turnouts; and the five-year survival-rate was 14%. Radical resection was undertaken in all patients with A, B, or C lesions, and the age-corrected survival-rate was 82% at five years. The "no-touch isolation" technique was of greatest benefit to patients with stage-C lesions (metastases to regional lymph- nodes, but no clinical or radiological evidence of distant spread), for their five-year survival-rate was 67%, compared with 28% in those treated by con- ventional techniques. ~. e

1. Turnbull , R. B. Jr., Kyle, K., Watson, F. R., Spratt, I. Ann. Surg. 1967, 166, 420.

2. Turnbull , R. B. Jr., Kyle, K., Watson, F. R., Spratr~ J. h~ Abdomio hal Operations; vol. ~I (edited by R. Maingot). New York, 1969.

3. Tyzzer, E. E..7. reed. Res. 1913, 28, 309. 4. Cole, W. H., Packard, D., Southwick, H. W. J . Ant. ,ted. Ass. 1954,

155, 1549. 5. Fisher, E. R., Turnbull , R. B. Jr. Surgery Gynec. Obstet. 1955, 10O,

102. 6. Turnbull , R. B. Jr. ,'Inn. R. Coll. Surg. Engl. 1970, 46, 243. 7. Butler, E. C. B. Bull. Sac. int. Chirurg. 1968, 5, 1. 8. Goligher, J. C. in Surgery of the Anus, Rectm~ and Colon. London,

1967. 9. Smiddy, F. G., Gollgher, J. C. Br. reed. J. 1957, i, 793.

10. Cutler, S. J., Laurie, W. L Nam. Cancer lnsr. Mono&r. 1963, no. 15,