31

what it thinks good. On the other hand, when a pro-fession goes into partnership with the State for a purpose,we cannot reasonably count on the new ideas comingfrom the administrators, and the experiment of partner-ship is unlikely to succeed unless the profession itselfprovides them. New ideas-especially in a world sonew as this-occur mostly to the young; and what is sodisquieting in the present state of our profession is thatthe young seem so often dissatisfied with their oppor-tunities-a different matter from their deficient pay.All too clearly the system we have evolved for appointingconsultants means that too many young men are too longobliged to follow too conventional a path; and far toomuch depends on their pleasing their chiefs. On paperthat system looks as wise and fair as anyone could wish;but it has been vitiated, in medicine and surgery at

least, by a degree of competition such that nobody hasmuch chance of getting an appointment unless hesecures the active support of the people at the teachinghospital for whom he has worked. This dependence onintraprofessional patronage must often weaken indivi-duality and strengthen orthodoxy6; and, though theremay be no way of avoiding it so long as competitionremains at its present pathological level, all concernedshould at least be on their guard against the danger ofinhibiting or suppressing or alienating what is fresh.Even in our professional organisations-in the manage-ment of medical societies and the like-the duties and

pleasures of office too often go to those who have hadthem before. With an ageing population we seem tohave an ageing profession; and though the wisdom ofage can be valuable the enthusiasm of youth is at least asprecious and far more easily lost. FRANCIS BACON wasnot enormously impressed by the contribution of youngmen to public affairs: they are, he said,

" fitter to inventthan to judge, fitter for execution than for counsel, andfitter for new projects than for settled business ". Buthe was equally alive to the deficiencies of the old:" Men of age object too much, consult too long, adven-ture too little, repent too soon, and seldom drivebusiness home to the full period, but content them-selves with a mediocrity of success ". Could these

tendencies, within our profession, explain some of theslightly calcified appearances in the N.H.S. ?Never have changes in knowledge and techniques been

so quick, and at such times it is well to remember lessonsfrom the past. But assured leadership can come onlyfrom those who are at home in the present-in the worldof today and tomorrow. And these are seldom the

people who were at home the day before yesterday.

6. ibid, 1958, ii, 1172

Penetrating the Homograft BarrierTHE time is coming when surgeons will have recourse

regularly to the use of tissues and organs taken from adonor in order to make good the effects of injury ordisease in their patients. A good deal of this is alreadybeing done-for example, with blood and cornea, whichare necessarily alive during and after transference

_ (homovital, grafts), and with bone and artery trans-plants, which need not be alive, provided their proteins

are in a fresh or undenatured state. Skin, too, is inconstant demand, though it is less often used as a

homograft than would be expected. It may be that

extensively burned patients, whose need for skin coveris the greatest, are such a problem in other ways thatsurvival of skin homografts applied to them is an

academic problem-even though it has been repeatedlyshown that such homografts can survive in the recipientfor three weeks or more. MEDAWAR 1 proved experi-mentally that the basis of homograft rejection was thedevelopment in the recipient of antibodies to the cells ofthe donor, and that the application of a second set ofgrafts from the same source is followed by more rapiddisintegration of them than of the first set. Moreoverif other cells, such as leucocytes, were offered in the firstinstance, subsequent skin grafts from the same animalunderwent early failures. 2 This does not happen if

spermatozoa from the same donor are used instead of

leucocytes.3 3

Many attempts have been made to modify the homo-graft response since this was shown to be due to animmune response depending on the intimate com-

munication, through blood-vessels, of the antigenproduced by the graft cells with the reticuloendothelialsystem of the recipient. Where the graft can be main-tained in isolation, yet kept nourished by extracellularfluid, the graft can be expected to survive indefinitely.Corneal grafts and experimental homografts to theanterior chamber are examples; and in mice ALGIREet al.,4 using specially designed inert plastic containers,permeable to tissue fluids yet not to cells, have main-tained homografts elsewhere in the body. In agamma-globulinxmia in man, the homograft reaction is weakor even absent.5 The homograft barrier has been trans-cended in other ways. Normally homografted humancancer cells are rejected, as would be expected, withinthree to four weeks; but if the recipient is a patient withadvanced cancer this period is significantly longer-even as long as six months. In both types of recipientinduced immunity has been demonstrated. 6 Whereintimate connection must be established between thecells of the two organisms concerned-for example,in organ transplantation requiring blood-vessel anasto-mosis, or where the donor cells have to be administeredintravenously-the reaction may possibly be retardedby depressing the reticuloendothelial response in therecipient. This has been attempted in various ways,including either administration of corticosteroids - or(more potent but more dangerous) high-dosage total-body radiation.One result of such radiation is profound depression

of the blood-forming tissues with resulting ansemiaand impaired resistance to bacterial invasion. Other

foreign proteins are accepted; and as long ago as 1950DEMPSTER et al. showed that homologous skin grafts1. Medawar, P. B. J. Anat., Lond. 1944, 78, 176.2. Medawar, P. B. Brit. J. exp. Path. 1946, 27, 9.3. Voisin, G. A., Toullet, F., Maurer, P. Ann. N.Y. Acad. Sci. 1958,

73, 726.4. Algire, C. H., Weaver, J. M., Prehn, R. T. ibid. 1957, 64, 1009.5. Good, R. A., Varco, R. L., Aust., J. B., Zak, S. J. ibid. 1957, 64, 882.6. Southam, C. M., Moore, A. E. ibid. 1958, 73, 635.7. Dempster, W. J., Lennox, B., Boag, J. W. Brit. J. exp. Path. 1950,

31, 670.

32

survived longer if the recipient had previously beenirradiated. From this it might have been concluded thatreticuloendothelial cells infused into severely irradiatedanimals would repopulate their aplastic marrow; butearly work on protection by spleen implants led to.the idea that some chemical or humoral agent wasgiven with or came from the cells of the implant: it wasonly slowly realised that, in the absence of bone-marrowactivity in the recipient, true cellular replacement wasbeing achieved. This was brought to light by labellingthe donor cells. PORTER and MURRAY 8 found that

65% of male rabbits, subjected to 1100r whole-bodyradiation and infused later with female rabbit marrow,showed female circulating blood-cells subsequently.Protection by heterologous cells against lethal bodyradiation had been reported earlier; and these curiouspreparations became appropriately known as radiationchimxras. Turkey-chicken, rat-mouse, and other com-binations have been described.9 But further diffi-culties arose. The chimaeras did not continue to thrive.Even mice with surviving mouse-marrow implants alldied within four months, of what came to be called" secondary disease ". First thoughts were that thismight be due to renewal of the host’s ability to reactagainst the foreign cells, but now it is believed that theopposite occurs: the grafted cells may be reactingagainst the host.1o It therefore became necessary to

provide donor cells which were incapable of reacting.For many years it has been known that embryonictissues may provoke a slighter homograft responsethan does adult tissue; and BILLINGHAM et al.11 have

conclusively shown that under some circumstancesfoetal tolerance of homologous grafts is high, and can beindefinitely maintained. If, then, a graft of foetal cellsuspension is well tolerated, and the secondary diseaseis due to the graft’s own reaction to its host, suchfoetal cell population within the marrow of the hostshould not be so liable to react unfavourably as adultimplants usually do. (Even embryo recipients can

suffer if adult homografts are added in excess of theestablished safe dose, producing the so-called " runtdisease " in the young animal after birth.12) Such a

possibility is now being investigated, and at HarwellBARNES et all have found that, using embryo spleenand liver, about a half the animals treated survived forthree months, after which time all the controls weredead. Marrow cells stored by suspension in glycerinand freezing at -79°C are known to protect against fatalirradiation,14 so that the prospect of providing a store ofan effective agent, in the form of frozen embryonictissues, for treating irradiation casualties would seem tobe reasonably bright. There already have been a fewreports of the clinical use of bone-marrow infusions inthe treatment of hypoplasia, 15 16 and in Paris the8. Porter, K. A., Murray, J. E. J. nat. Canc. Inst., Wash. 1958, 20, 189.9. Lancet, 1958, i, 892.

10. Trentin, J. J. Proc. Soc. exp. Biol., N.Y. 1956, 93, 688.11. Billingham, R. E., Brent, L., Medawar, P. B. Nature, Lond. 1953,

172, 603.12. Billingham, R. E., Brent, L. Transplantation Bull. 1957, 4, 67.13. Barnes, D. W., Ilbery, P. L. T., Loutit, J. F. Nature, Lond. 1958,

181, 488.14. Porter, K. A., Murray, J. E. Cancer Res. 1958, 18, 117.15. Humble, J. G., Newton, K. A. Lancet, 1958, i, 142.16. Thomas, E. D., Lochte, H. L., Lu, W. C., Ferrebee, J. W. New Engl. J.

Med. 1957 257, 491.

successful treatment in this way of five severely irradi-ated patients has been reported in the lay press.l’A good deal of DEMPSTER’S work on the homografting

of kidneys has been concerned with elucidating thereaction between the two individuals concerned, and hewas one of the first to point out that the grafted kidneywas able to react against its host.18 The clinical applica-tion of this operation has been limited, even though, asHuME et al.19 at the Peter Bent Brigham Hospital havepointed out, the transplanted kidney in man can

function quite effectively for very much longer than inthe dog. From the same centre now comes an account 20of seven cases of renal transplantation for hopeless andadvancing uraemia. In this group there was no risk of

homograft reaction because in every case the patientwas one of a pair of monovular twins; the donor kidneywas offered by the healthy member of the pair. Sixof the patients were rapidly relieved from their illnesswith a large diuresis, the arrest of convulsions and ofheart-failure, and the partial relief of hypertension.Once the third kidney was established, the patients’two diseased kidneys had to be removed. In only onecase did the original disease reappear in the trans-

planted kidney, with a fatal outcome-though in oneother there was evidence suggesting that the transplantwas becoming affected. On the other hand, one of thepatients has successfully completed a normal pregnancy.The care and thoroughness with which these patientswere treated and studied has yielded without doubtknowledge which will bring closer the day when surgeryof this kind becomes established.

17. Daily Telegraph, Nov. 22, 1958.18. Dempster, W. J. Brit. J. Surg. 1953, 40, 447.19. Hume, D. M., Merrill, J. P., Harrison, J. H., Thorn; G. W. J. clin.

Invest. 1955, 34, 327.20. Murray, J. E., Merrill, J. P., Harrison. J. H. Ann. Surg. 1958, 148, 343.

Annotations

A HANDFUL OF SILVER

TEN years ago many honest doubters overcame theirhesitation and decided to support the National HealthService because it had at least the great merit of removingall financial barriers between the doctor and the patient.Since then certain small hurdles have been reluctantlyreplaced, and most patients now have to pay somethingtowards dental treatment, for some appliances, and fortheir prescriptions. Probably no-one feels entirely happyabout these charges. Though their introduction was feltto be justified if it averted cuts in the service which mightotherwise have been required by anxious Chancellors,they are apt to fall most heavily on people who canleast afford them.

Naturally enough, all the charges are disliked; but thoseon appliances and dental treatment have roused less resent-ment than those on prescriptions-perhaps becauseappliances are usually not such a regularly recurring needas medicine, and because the dental charges have donesomething to safeguard the needs of the priority groups ofyoung children and expectant mothers. Thus controversyhas always been greatest over the comparatively modestprescription charge. The reasons are not far to seek.

Though the charge is small, almost everyone has paid it at