Some British contributions to tropical medicine

158 PAPER

SOME

BRITISH

CONTRIBUTIONS MEDICINE

TO

TROPICAL

BY

Sir HAROLD SCOTT, K.C.M.C.,M.D., F.R.C.P., B.P.H., D.T.M. & H., F.mS.ED.

When I was first approached and invited to deliver this address I wisely declined, feeling it to be beyond my powers, but I was told that if I would not do it the authorities might have some difficulty in finding a substitute. The flattei:y worked and I agreed to do my best. W h e n I began to collect notes, the subject loomed ever larger ; it seemed a hopeless task to try in one short hour to do anything like justice to so vast a subject, but it was too late then to withdraw. It is a well-known fact that the English--perhaps it would be wiser to say the British, in order not to give offence to our friends beyond the border--the British, then, are the most retiring, diffident, modest and self-effacing of nations, so you will understand how much it goes against the grain to seem to boast of our achievements in the advancement of knowledge of disease in the tropics. But, after all, this i s the Festival of Britain and, consequently, a suitable time for telling the world what Britain has done for the promotion of general and personal health and for medical research in tropical countries. It is true we are deeply sensible of the fact that men of other nations have played a part ; to tell of these would need a course of lectures, so I am restricted to relating the achievements of British workers, which must not be taken to imply ignorance of, or failure to recognize the work of, others. No man liveth unto himself, and British achievements have often been based on the work of others, as more often still has the opposite been the case and foreign workers have built on British foundations. W h e n we come to think of it, we are safe in saying that Britain and the British Commonwealth of Nations own and are responsible for a good deal of the tropical and subtropical world and, therefore, have had better opportunities than most for observing conditions and putting into practice the results of research into these conditions. The first question that arises is, " Where are we to start ? " and the customary answer to this question is, " At the beginning, of course." I might, therefore, start by telling briefly of the state of things in some of the places we colonized, or ruled over, or settled in, but I think we must go even a little farther back, to the days when we had to pay attention to the health of our seamen and soldiers in tropical climates, for it was in looking to the conditions of life and the health of the inhabitants of those countries that the foundations were

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laid on which was built the superstructure of research into special conditions inimical to health, i.e., tropical medicine. Let us not, then, forget to honour the men who, with the limited knowledge of their day, did so much for those for whose health and well-being they were responsible. We are sometimes tempted to look with ridicule on the quaint views of bygone years, but let us remember at the same time that future generations will of a surety ridicule some of the tenets we hold dear today ; nothing is more easy, or more foolish, than to censure one age for not possessing the mental equipment of the next. As I have written elsewhere : " Science is truly international and knows no boundaries of nations, languages or creeds. The advancement of knowledge in the causation and prevention of disease is not for the benefit of any one country, but for all for the lonely African, deserted by his tribe, dying in the jungle of sleeping sickness, or the coolie sflticted by the miseries of beriberi, just as much as for our own citizens." All honour, then, to men like Sir GILBERT BLANE (1749-1834), THOMAS TROTTER (1760-1832), JAMESLIND (1716-1794), Sir WILLIAM BURNETT (17791861), BRYSON, and laymen such as Sir JOHN JERVIS, Admiral Sir VESEY HAMILTON and Captain COOK. It is a truism now, but was not in the days when BLANE averred that it is much less expensive to keep sailors healthy than to pay for repairing the ravages of disease--fevers, fluxes, scurvy and ulcers --ascribed by him, rather vaguely we must admit, to the nature of the diet and the malignant influence of the climate. He it was who stressed the evils of pressed men introducing into ships typhus and relapsing fever, brought by the dregs of humanity from the gaols ; men being carried on board bound hand and foot, while the band played " Who are so free as the sons of the sea ? " Then consider their quarters on board, over the holds with stagnant water and bilge, breeding mosquitoes conveying malaria and yellow fever. BLANE'S precautions for preventing and avoiding sickness among sailors could hardly be bettered even today and the need for foods, now known to be invaluable for their vitamin content, for preservation of health and accelerating convalescence --dried fruits, barley, rice, sago, eggs, carrots, green vegetables, lemons, oranges, etc.--are among other recommendations put forward in his Memorial to the Board of Admiralty in 1781. Then we have JAMES LIND, many of whose recommendations, made at the time on empirical grounds, found scientific confirmation a century or more later. We read, in his Precautions in Southern Climates, of the importance of anchoring vessels away from swamps and avoiding night air, screening and the use of " bark " morning and evening ; in other words, warding off mosquitoes and the use of quinine prophylaxis. He wrote much on scurvy in the Navy (1754); his methods and recommendations were applied with success by Captain COOK 20 years later; nevertheless, 90 years were to elapse before lemon juice w'as made a compulsory issue in the British Navy. THOMAS TROTTER did much to improve the conditions of service and to guard against

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introduction of disease, culminating in his work, Medica nautica, published at the beginning of the nineteenth century. He and BRYSON found timely and able support from Sir WILLIAM BURNETT, and it was at BURNETT'S suggestion that BRYSONwrote his work on the Climate and Principal Diseases of the African Station. BURNETTwas then Medical Director of the Navy and in 1827 made arrangements for the instruction of naval medical officers, but 44 years passed before the school was started at Haslar for teaching general and naval hygiene and 20 years more before the study of tropical medicine was added. it would not be fair to pass unnoticed the benefits, from the medical point of view, conferred by Captain COOK, himself a layman. In the first of his three famous voyages, in the Endeavour, a vessel of 370 tons only and a complement of 84, he had no sickness on board until they reached Batavia, where many fell ill with dysentery. Batavia had at that time a bad reputation on account of dysentery and typhus, so-called but probably typhus abdominalis or enteric fever. Generally, in those days a voyage of 3 months meant almost invariably an outbreak of scurvy, but COOK, on his second voyage, had only three men on the sick list and only one with scurvy. He had supplied the crew with scurvy grass (Cochlearia officinalis), celery and other vegetables and " sweetwort." In the sister-ship, the Adventure, no such precautions were taken and many fell sick with " scurvy and flux " but recovered when given " the wort, marmalade of carrots and rob of oranges and lemons." On his third voyage he found another antiscorbutic, berries at Samganoodha harbour. He also carried a supply of Peruvian bark for crews " exposed to unwholesome climates." Incidentally, COOK obtained drinking water, on his second voyage, by distillation of sea-water. This was in 1772-1775, and though Dr. CHARLES IRVING received a reward of £5,000 from Parliament for doing the same thing, he was by no means the first, for not only COOK but LIND had done it before him and both had been forestalled nearly two centuries by Sir RICHARD HAWKINS who, in 1593, writing of the voyage of the Dainty, says : " In the passage to Brazil our fresh water had failed us many days by reason of our long navigation, yet with an invention I had in my ship I easily drew out of the water of the sea sufficient quantities of fresh water to sustain my people with little expense of fuel; for with four billets I stilled a hogshead of water and therewith dressed meats for the sick and hale. The water so distilled was found to be wholesome and nourishing." We have seen that sailors were liable to suffer from diseases introduced by " prest " men, from those due to dietetic errors and vitamin deficiencies on long voyages as well as from visits to tropical climates and poor and unhygienic accommodation on board, but soldiers ran an even greater, though different, risk, from having to stay and fight on a possibly inhospitable shore and to penetrate into the interior. At the same time, any with an inquiring mind would have a better opportunity of studying the local diseases. Hence we

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find, as we would expect, army medical officers doing excellent work in elucidating obscure tropical conditions. The list of those who have added thus to our knowledge is a long one, from Sir JOHN PRINGLE (1707-1783) to Sir NEIL HAMILTON FAIRLEY and to J. S. K. BOLD, who has contributed much to tropical pathology and to the clarification of the vexed subject of bacillary dysentery, the scourge of armies in the field for so long. MONRO, ROBERTJACKSON, BELL, HUNTER, MOSELEY, Sir JAMES MCGRmOR, Sir RANALD MARTIN, Sir ANDREW HALIDAY, EDMUND PARKES, Sir DAVID BRUCE, Sir WILLIAM LEISHMAN, Sir WILLIAM MACARTHUR are others worthy of mention. It is not possible in the time at our disposal to tell of all that these have done ; we can only give a passing reference to a few of the more important. PRINGLE spent a good part of his service in Flanders ; nevertheless, in his work on Diseases of the Army in Camp and Garrison there is much that is applicable to the tropics, and he adumbrated many discoveries of more than a century later. He stressed the importance of establishing camps away from marshes ; he made distinction between tertian and quartan fevers and those with " double paroxysms " ; the 3 weeks' remittent or intermittent fever with lenticular spots (typhoid) and 14-day fever with petechiae or blotches and ending in crisis (typhus) and the West Indian fever with jaundice and black vomit (yellow fever), and he anticipated a form of treatment of bacillary dysentery by concentrated saline, which we thought was a new discovery during the war in South Africa. He refers also to a spotted fever with pus in the cerebral ventricles and at the base of the brain (cerebrospinal fever) and to " malignant fever with carbuncles from killing and eating diseased cattle " (anthrax). ROBERT JACKSON (1750-1827) deserves special mention because of his Treatise on the Fevers of Jamaica, published in 1791, and his work on febrile diseases among the British Army in the West Indies, published in 1817. Others do not call for detailed mention because they were concerned with the benefits to soldiers and the maintenance of health by general measures, such as Sir JAMES RANALD MARTIN, who wrote on the hygiene of camps, the dangers of marshes, the deleterious effects of fatigue on health, the hazards from accumulation of filth in camps. Also Sir ANDREW HALIDAY, who was Deputy InspectorGeneral of Army Hospitals, and wrote in 1839 on sickness and mortality among troops in the West Indies, on the dangers of siting camps near swamps--he had vague ideas on marsh miasma and the close sealing of shutters at night to keep out miasma and mosquitoes. EDMUND PARKES (1819-1876) also wrote much on Army hygiene and in particular on overcrowding and the spread of tuberculosis and respiratory disease. " We are fully justified in saying that advances in military hygiene have not benefited the Army alone ; the benefits to.science have been mutual and reciprocal. The needs of the Army stimulated research and the results of research conferred blessings inestimable on the Army " (Hist. of Trop. Med., 1, 61) ; to mention only one, the use of prophylactic vaccine in enteric fever originated by Sir ALMROTH WRIGHTin the South

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African War, a time which might be regarded as the beginning of the scientific study of disease in the field. Britain, owing to her insular position, has been much stimulated to explore and colonize, for this position, per se, invites, nay demands, commerce for expansion. The British have always been adventurers, a mixture of Angle, Saxon, Jute, Dane, Norwegian, Flemish and others. Their list of intrepid explorers includes FROBISHER, GILBERT, WILLOUGHBY, DAVIS, CHANCELLOR, HAWKINS, DRAKE, RALEIGH and CooK, and, in more recent times, MUNGO PARK, OUDENEY, CLAPPERTON, LANDER, LIVINGSTONE, STANLEY, CAMERON~ MARY KINGSLEY. MUNGO PARK speaks of yaws, elephantiasis and leprosy among the African negroes, in 1799 ; also of guinea-worm infestation. Down to the early years of the present century West Africa had a very bad reputation --monotony, drink and disease cutting short many a promising career. In a Handbook of Useful Information was a chapter on " How to Reach West Africa and How to Return," and Part II begins with the impressive, if ungrammatically expressed, statement on the return, " If dead, this will not be needed." Further, a warning was issued to officials and immigrants telling them that they must expect to suffer from : " Shivering, lassitude, headache and backache. Cerebral excitement with raving delirium. Liver deranged--constant vomiting. Vomiting of blood. Chronic haemorrhage, blackwater, shivering and rigors. Sunstroke with staggering and unconsciousness. Acute dysentery. Asiatic cholera. Acute jaundice. Typhoid." Great, indeed, have been the difficulties in the development of our African colonies. Reeking marshes, insect-haunted, forests dense and almost impenetrable from matted growth of creeper and thorn-bush, mud-silted rivers impeding transport, huts built for protection soon invaded by flies, mosquitoes, ticks, spiders and scorpions. Many have lost their health and not a few their lives in these explorations: LEYLAND perished in exploring the Niger, HORNEMAN disappeared, his fate unknown; LucAs returned an invalid, HOUGHTON died of starvation, when trying a western route from Senegal; MUNGO PARK, reduced by sickness and privation, drowned in trying to escape from hostile natives; CLAPPERTON dying in Hausaland, LANDER in Fernand~ P6. We shall refer later to medical workers who fell victims to tropical research. It is strange, and worth noting, how disease in East Africa has changed since LIVINGSTONE'S day. The prevailing diseases then, according to his account, were pneumonia, rheumatism, heart disease, smallpox (on the coast but not inland), whooping cough, dysentery and ophthalmia. He specially remarks on the absence of cancer and cholera, consumption and scrofula (tuberculosis had, at that date, hardly been introduced ; later its ravages were severe). Negro lethargy is barely mentioned though he knew the tsetse fly well, and STANLEY notes that its bite caused the deadly nagana in horses and donkeys. Both

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LIVINGSTONE and STANLEY thought it harmless to man and the former would watch it bite him undisturbed. One last word before we pass on to tell of the achievements of individual workers in the advancement of tropical medicine. The development may be said to have passed through three stages. In the first, early colonizers went out to establish trade for their own advantage, and medical men accompanied them to attend them when sick ; in the second, precautions would be taken to safeguard the colonists from incursion of disease from the natives in their vicinity, working for and with them ; in the third, a study of these diseases would be undertaken with a view to eradication of disease among the natives. To attain this end medical, agricultural and educational authorities work together, the first studying the causes and prevention of infection and together with the others inculcating the principles of hygiene, raising physique by better balanced diet, better housing, schemes for maternity and child welfare. Research teams are sent out to investigate special diseases, plans are made for co-ordination of research, laboratory services are increased. It must have been difficult to decide where to start when conditions such as the following existed, as in Bombay in 1861 : " Go into the native towns and around you you will see on all sides filth immeasurable and indescribable, and at places almost unfathomable ; filthy animals, filthy habits, filthy streets and with filthy courtyards around the dwellings of the poor; foul and loathsome trades, crowded houses, foul markets, foul meat and food, foul wells, tanks and swamps [the Commissioner's choice of adjectives appears to have been limited], foul smells at every turn, drains unventilated and sewers choked, and the garbage of an Oriental city. Men, women and children, the rich and the poor, living with animals of all kinds and vermin, seeing all this and inhaling the deadly atmosphere and dying by the thousand." Also : " The large mass of the people, living under the most primitive and insanitary surroundings, afforded an almost unbounded field for the spread of every kind of epidemic disease. Fevers, smallpox, plague and cholera each took a terrible toll from the unfortunate inhabitants who frequently looked upon them as a sign of divine displeasure to be averted by prayers and sacrifices, rather than by precautionary measures. The exact mortality caused by these diseases will never be estimated. Contemporary literature, however, leaves no doubt of their severity. Of an epidemic of relapsing fever one reads that ' of numerous native villages nearly the whole population was ill at one and the same moment ' and ' the banks of the river were covered with the dead and dying.' " The list of Englishmen who have taken part in initiating and furthering health measures in India is a long one, and if we include research workers who

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have influenced directly or indirectly disease in India the list would be still longer. Far be it from me to belittle the work of the majority, but special mention may be made of JAMES JOHNSON (1777-1845) and his work on malaria and cholera, of Sir JAMES RANALD MARTIN, of whom we have already spoken ; of Major G. M. J. GILES and his work on mosquitoes ; of Sir JAMES PARDEY LUKIS (1857-1917), a former Director-General of the Indian Medical Service, who did so much to promote research ; and in more recent times, Sir LEONARD ROGERS, Sir RICKARD CHRISTOPHERS, Sir JOHN MECAW, all of whom are happily with us and of whom, consequently, it is difficult to speak freely without being thought sycophantic. References to their work will be made later. It may interest the audience to hear of the duties and the pay of the medical officers in the early days of the Indian Medical Service. In the first half of the eighteenth century the Surgeon-General received £20 to £30 a year--about one-tenth of what a dustman gets now--and his duties included daily attendance " from morning until night, to cure any persons who may be hurt in the service of this company, and the like in all their ships . . . they shall also cut the hayre of the carpenters, saylors, caulkers, labourers and any other workmen in the companies said yards and ships, once every 40 days, in a seemly manner." Can you imagine Sir LEONARD ROGERS cutting the hair of the carpenters and labourers in a seemly manner for a maximum pay of £30 per annum ? If I had time I might tell of the research institutes, the establishment of hospitals, the setting up of Sanitary Commissions, the founding of colleges and schools for medical education in India, Ceylon, Africa, Hongkong and Fiji by British officials and staffed by British medical men, but I have not, and I feel sure it would be more interesting to tell of the accomplishments of individuals in the many fields of tropical medicine and medical research. Let us begin with malaria, the most widespread and most devastating in times past of all tropical diseases. We must bear in mind, however, that malaria is by no means strictly tropical, for it is found on the Continent and in Russia, the United States and even in England. It is known to have killed King JAMES I and CROMWELL, and King CHARLES II suffered severely from it, but its greatest ravages are in warm climates. In the long history of this disease British names stand out pre-eminent. SYDENHAM(1624-1689) and, after him, RANALDMARTIN, PRINGLEand BRYSON,separated the different forms of the fever, on clinical grounds ; CHISHOLMdifferentiated malarial bilious remittent fever from yellow fever; RO~ERS, in 1898, noted the association of ground water and malaria prevalence. Further advances were made when STEPHENS and CHRISTOPHERSdemonstrated that in malarious districts children often harboured the parasite without showing any symptoms and so constituted an indigenous reservoir. In solving the problem of transmission Englishmen have played no small part, but they were a long way from being the first. This honour must be accorded to COLUMELLA, who as far back as A.I). 100 observed a

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connection between marshes, insects and fever, and LIND (1716-1794) advocated safeguarding from marsh miasma, while JOHNSON in 1818, MACCULLOU~H in 1827, and W. J. EVANSin 1837, all pointed out the use of mosquito nets, gauze veils and curtains as protecting against malaria by keeping off mosquitoes. Sir PATRICK MANSON was, however, the first to prove that insects could cause disease by conveyance of infection, by his observations on filaria embryos and Culex ifi 1879, and in 1894 he put forward the suggestion, on the analogy between filariasis and malaria, that the latter might be mosquito-borne and 3 to 4 years later Ross, at MANSON'S instigation, showed that the parasite of malaria had a double life cycle, sexual in the insect, asexual in man, and that the infection was not due to marsh air and miasma. The stage on which information was lacking, that between infection and the onset of symptoms, described by S. P. JAMES in avian malaria as the exoerythrocytic phase, was explained as occurring also in human malaria by the researches of Professor H. E. SHORTT and P. C. C. GARNHAM. ROSS, it is true, finding difficulties in the scarcity of human cases, carried out much of his work with avian parasites. Again and again he lost heart but resumed at MANSON'S encouragement, and MANSON'S tact and patience must have been sorely tried in dealing with a man of Ross's peculiar temperament. Later, Ross did much by visits, investigations and advice to assist in combating malaria in various parts of the world, in Mauritius in 1907, in Cyprus in 1913, Alexandria in 1915, Salonika (or, as the B.B.C. will persist in calling it, Saldnika) in 1917-1918, Ceylon in 1926, and Malaya in 1927. In 1901 the Royal Society of London sent out a Commission to study its cause and control, and two of its members, J. W. W. STEPHENS and RICKARD CHRISTOPHERS, have since gained a worldwide reputation, and the final proof may be said to have been reached when SAMBON, TERZI and G. C. L o w (the last of whom has occupied the Presidential Chair of the Royal Society of Tropical Medicine and Hygiene and is, happily, still with us) lived in a mosquito-proofed hut in a highly malarious locality of the Roman Campagna and remained well though the peasantry around suffered heavily. Further advances have been made by the survey work of Colonel J. A. SINTON, V.C., and Sir GORDON COVELL. Englishmen have also played a part in the discovery of the actual causa causans, though perhaps the less we say of that the better, for much of it was wrong, such as MASSEY of Ceylon and his microscopic fungus ; HOLDEN, who backed this up by saying that the fungus plus H2S from decay caused malaria ; DUDLEY OWEN, of Rhodesia, who claimed to have grown the " malaria bacillus " from grave soil. But DELAFIELD in 1872 really seems to have forestalled LAVERAN'S discovery in 1880, for he describes in his Handbooh of Postmortem Examinations and of Morbid Anatomy small particles of black or reddish pigment in the blood of malaria patients, as granules embedded in small, irregular, transparent, finely granular bodies ; but to LAVERANremains the credit of grasping their significance. Moreover, DELAFmLD himself was forestalled by

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HE1NRICH MECKEL who, in 1847, found pigment in the blood and organs of patients dying from malaria. In the matter of treatment, much has been done by the British. R. BRADY, Professor of Physick of Cambridge University, and after him SYDENHAM, did much to popularize the use of Cinchona, ROBERT TABOR'S " secret remedy." It was CHARLES LEDGER, a London merchant, who forwarded Cinchona seeds to England and was afterwards killed by natives in South America; its cultivation in India was largely due to the efforts of Lady CANNING, wife of the Viceroy. This part of our subject cannot be left without telling of the epochal work of Brigadier (now Sir NEIL) HAMILTON FAIRLEY on the suppressant effect of mepacrine in malaria, especially malignant tertian, so that men can continue to do hard physical work in spite of exposure to arduous conditions and constant infection, as soldiers on active service in the Pacific and the Far East in the Second World War. I give Sir Nell's conclusions in his own words for they express them better than could any paraphrase of mine : " The military implications of these experiments were considerable, for they showed that non-immune troops on a correct atebrin regimen could be brought into hyper-endemic areas of malaria and be engaged in the fighting in the jungle for many months with an absolute minimum of malaria casualties. Since gametocytes never appeared in the blood there would not be malaria carriers in the force, and as malignant tertian malaria was cured, there should be no deaths and no blackwater fever; the only problem which remained was that of latent benign tertian malaria which would produce overt attacks a few weeks after atebrin suppressive treatment ceased." HAMILTON FAIRLE¥ is also responsible for much original research on the relative effectiveness of various drugs--mepacrine, sontochin (nivaquine), chloroquine, paludrine and others--in the treatment of malaria. Compare this with the treatment which CHISHOLMclaimed as so successful at the beginning of last century: Copious bleeding, three pounds of blood being taken away and repeated if the disease persists ; cold affusion and calomel up to 30 grains every 3 hours to produce ptyalism and purging. Two hundred and forty grains of calomel in the 24 hours should do that all right, but how the unhappy patient must have prayed for death i The studies of WARRINGTON YORKE and his colleagues on synthetic antimalarial products and the results of their use recorded by ADAMSand MAECRAITH in Liverpool and by FAIRLEY in London are of the utmost importance, and I wish I could do more than thus briefly refer to them in this sketch, but time forbids. Another tropical disease of importance, to the solution of which British investigators have contributed much, is Plague. Though now to a great extent tropical, it was not always so, as all will call to mind the Black Death of the

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fourteenth century and the Plague of London of 1665. Its chief home is India, and in the last 5 years of the nineteenth century and the first 20 years of the present it was estimated that more than 11,000,000 deaths occurred in that country from plague. It was also common in the Colonies and Dominions, in Ceylon, South Africa, Kenya, Tanganyika, Uganda, the Gold Coast, and Australia. Though the honour of discovering the causative organism fell to a Swiss bacteriologist, YERSlN, the discovery was made in a British Colony, Hongkong, and many problems in its aetiology have been solved by British workers. The connection between rats and plague had long been known, or at least suspected, and ASHBURTONTHOMPSON'S expressed opinion in 1901 that rats played an important part in dissemination was by no means new. As far back as A.D. 610 the Chinese term for plague was Shu-yi, that is, " rat pest." LowRY, at Pakhoi in 1882, and RENNIE, at Canton in 1894--the year of YERSlN'S discovery of the bacterium in rats and man in Hongkong--had noted the association of rodents and plague. Questions calling for answer were: How did the infection pass from rat to rat, and from rat to man ? The observation was made by a Japanese, OGATA,that rats, dead and cold, could be handled with impunity, but not those freshly dead and still warm, and that the latter were infested with fleas whereas the former were not. Then, in 1898, SIMOND, in Bombay, who had made the same observation as OGATA,produced plague in mice by inocnlating them with an emulsion of fleas from a plague rat, and TIDSWELL 2 years later found the bacteria in the stomachs of fleas from infected rats. I will not take up your time by describing the ingenious experiments by which GLEN LISTON, at the Bombay laboratory, and, in 1905, the members of the Indian Plague Commission, GLEN LISTON, LAMB, PETRIE, ROWLAND and others, and later the Research Commission under Sir CHARLES MARTIN, proved that it was not the rat itself but its ectoparasites, fleas, which transmitted infection. Other names worthy of mention are Sir LEONARD ROGERS, who showed that climate, temperature and humidity played a part in its epidemiology ; FABIAN HIRST. for his work on Xenopsylla astia as vector in place of the common rat flea, Xenopsylla cheopis, in Ceylon ; of the use of the serum prepared at the Haffkine Institute for treatment of the disease and, later, in 1936, SOKHEY, MAUR1CE and NORMAN WALKER on the use of Haffkine's vaccine. Cholera is yet another of those diseases which today we are inclined to call "tropical," because improved modes of living and sanitary measures have largely excluded it from non-tropical countries, but it has not long been so. As late as the mid-nineteenth century it swept over Europe as a pandemic ; in fact, there were four pandemics between 1817 and 1865, raging respectively for 6, 11, 17 and 10 years, a total of 44 out of the 48 years. Cholera is probably the most awe-inspiring of all pestilences, striking unexpectedly in the midst of health and killing in a few hours. Again and again has the fear of cholera been the beginning of sanitary wisdom, and early public health legislation in Great Britain owes much to cholera.

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With a few exceptions, workers in temperate climates may be said to have done more than those in the tropics towards the elucidation of cholera problems, but here, too, many of the discoveries and advances are due to British investigators. From the epidemiological aspect, JOHNSON, in his book on Tropical Climates (1813), noted how pilgrimages and fairs in India favoured the origin and fostered the spread of infection. FARR, ACLaND, SUTHERLANDand SNOW all supported the water-borne theory of infection and the last-named proved its correctness in the Broad Street Pump epidemic at Westminster in 1854. JOHN MACPHERSON, Inspector-General of Hospitals in India, discussed contagion, direct and indirect, air, water, soil, season and weather and, hitting at BRYDEN, who supported the water-carriage idea, wrote: " The school that believes in the propagation of cholera mainly by water polluted by its germ is essentially English " (one need hardly say that MACPHERSONwas a Scotsman). JAMES KENNEDY contributed more concrete facts in 1832 in his History of Contagious Cholera. CUNNINGHAM and BI~DEN had noted the relative immunitY of Sepoys, and ROCERS the connection of rainfall and humidity with the epidemiology of cholera, in 1926, developed by him and Sir JOHN MECAW in their book on Tropical Medicine (1930). Others deserving mention are Surgeon-Major N. C. MACNAMARAwho, in 1866, postulated the entry of germs into the intestine by way of water, but was refused by the India Office to be allowed facilities for proving his thesis --the vibrio was not discovered until 1883--and NICHOLAS, writing to The Lancet in 1873 incriminated flies in the Malta outbreak of 1849. But British contributions loom larger in the matter of treatment. The use of hypertonic salines by ROGERS, regulated by the specific gravity of the blood, was revolutionary, but he had been to some degree forestalled by LATTA, of Leith, in 1831, supported by RANALD MARTIN, in 1848; O'MEARA used the same method in India in 1908. But to ROCERS is due the explanation of the rationale of the procedure. T. H. BISHOl~ also used hypertonic salines, but he administered them intraperitoneally. HAEFKINEintroduced in 1893 his vaccine for treatment ; it was in 1919 that T. C. McCROMBIE YOUNG employed it prophylactically for coolies going to Bihar and Bengal from Assam, the same year in which A. RoY, cf Dublin University Mission, was using it in Chota Nagpur district. Bacteriophage was discovered by D'HERELLE and TWORT (the latter an Englishman and a fellow-student with me) ; its use in treatment was tried by the former and by ASHESHOV, but its employment prophylactically is largely associated with the name of Colonel J. MORRISON, of the Indian Medical Service. The prophylactic value of cholera vaccine has been shown recently in the Egyptian outbreak of 1947. We must not pass by without reference to what British investigators have contributed to the elucidation of diseases now classed under the term Avitaminoses. It is only right that they should have done so for, when all is said, avitaminoses or deficiency diseases are diseases of civilization. Natives living on the natural fruits of the earth may die of starvation if crops fail, but they

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do not suffer from the so-called deficiency diseases. The elucidation of their aetiology was not easy; the whole idea was so revolutionary. When positive causes were always postulated for disease it was difficult to conceive--nay more, it did not enter into man's conception--that " absence of a thing could cause disease " and that " causation could be prefixed by a minus sign." We have no time to dwell on vitamins and vitamin research, but we must briefly call attention to what British workers have done in solving the problems of avitaminoses in the tropics. In Elizabethan days, and even later, any voyage of more than 6 weeks was liable to present cases of scurvy and many an expedition of promise has been ruined thereby. In 1591 Sir RICHARD HAWKINS,admiral, pirate and slavedealer, noted in his voyages to Brazil the benefit, nay the necessity, of oranges and lemons in maintaining the health of his crew and in averting scurvy ; in A.D. 1600 lemon juice was a statutory issue in the East India Company's ships. WOODALL,in his Surgeon's Mate (1617), gives lemon juice a prominent place and JOHN WINHTROe, in 1631, advises his wife, when she was preparing to join him in America, to bring with her, for use on the voyage, scurvy grass. LIND'S experiments, carried out in 1747, with reputed antiscorbutics proved the value of lemons and oranges, and the success of Captain COOK'S voyages, due to the absence of scurvy among his crews, to which reference has already been made, was the result of measures based largely on the work of Lind. In 1793 JoaN HARNESS, Medical Commissioner of the Navy, was issuing citric acid and lemons to sailors of the Mediterranean Fleet, and in 1807 CHARLES CURTIS, a naval surgeon, was insisting on the importance of vegetables in the food of seamen. I have mentioned only British names. It is but fair to state that the Dutch had established vegetable gardens at ports of call in 1598, and P~RE LABAT speaks of the growing of salads in boxes of earth on board ships going to the West Indies. In spite of all this evidence on the importance of lemon juice, and though it had been in common use for some 50 years, it was not until 1844 that the issue was made compulsory in the British Navy. Coming to our own day, WILLCOX, HEHIR and SHEPPARD record more than 11,000 cases among European forces in the First World War, treated by germinating peas and beans and vegetable cultivation, and, according to A. F. HEss, many cases escaped recognition under the diagnosis of "infective purpura." To the questions of beriberi, pellagra and other avitaminoses, British workers have made certain contributions of note, but it is only fair to say that others, the Dutch in particular, have done more. Here it is to the former that my remarks are restricted, though in so doing I would not for a moment belittle the work and discoveries of foreign investigators, for much of the British work has been based on the discoveries of others. This is particularly true of beriberi. Beriberi has been known to the British in India for more than 100 years. BALFOUR wrote of it in 1847 among troops in Madras Presidency, KEARNEY

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noted it in Madras and in Burma in 1872 and FAYRERinAssam in 1880. CALHOUN, in Ceylon, and HAMILTONand MALCOLMSON,in Madras, noted that a stay of some months in a district elapsed before any symptoms appeared, a fact confirmed by STANTON, in Malaya, in 1910 as a minimum of 3 months. It might be politic, but not quite honest, to pass in silence the period of erroneous findings by British workers as regards the aetiology, but we need not dwell on our mistakes. I refer to the theories of H. M. JOINT, of Fiji, of P. T. CARPENTER,of British North Borneo, on germs and parasites conveyed by cockroaches ; of MANSON and the inhalation of poison from the soil or the walls of infected houses ; of FRANCIS CLARK,of Hongkong, and its infectivity ; of D. C. REES who, in 1898, expressed the view that beriberi was a " place " and not a " food " disease, supported by CANTLIE in Hongkong and WATERHOUSEin his Army Medical Record in 1902. STANLEY,of Shanghai, was another upholder of contagion. Towards the end of the last century the idea of food in causation began to gain ground. Rice, or orizatoxin from bad rice, had been suggested as long ago as 1870, and HUNTER, in 1897, ascribed it to food--rice--infected by Staphylococcus albus. Other organisms incriminated were HAMILTON WRIGHT'S bacillus (disproved by Dudgeon), NOEL BARNARD'Ssporing bacillus, B. asthenogenes, and A. CANNON, who postulated a combination of three factors, this bacillus, endocrine disturbance and deficiency of vitamin B. This was in 1929 and was rather putting back the clock, for in 1907 W. L. BRADDONhad confirmed the work of EIJKMAN on the neuritis of birds fed on polished rice, and later, H. FRASER and A. T. STANTON (afterwards Sir THOMAS STANTON, Chief Medical Adviser to the Secretary of State for the Colonies) recorded analogous conditions in beriberi, supported soon after by the experiments at Kuala Lumpur lunatic asylum with rice, cured and uncured, and the classical tests with labourers at Negri Sembilan, the results of which were confirmed by EDIE, EVANS, MOORE, SIMPSON and WEBSTER at Liverpool in 1912. Others whose names should not be omitted in connection with this vitamin research are GOWLAND HOPKINS, HARRIETTE CHICK, MARGARET HUME, and, lastly, R. A. PETERS, Whitley Professor of Biochemistry at Oxford University, who has shown how complex is the vitamin B. We have already reached to B12 and this itself has several constituents. The last of the avitaminoses calling for detailed consideration is Pellagra, now mainly tropical in distribution. During the 150 years after the description by GASPAR CASAL,of Oviedo, in 1762, most reports came from South America, but in the early years of the present century cases were being reported in Britain by CRANSTONL o w (1909), SAMBONand CHALMERS(1912) and C. R. Box (1913). C. G. MANNING, in Barbados, had in 1910 recorded it under the name of psilosis pigmentosa. In the same year SANDWITH was advocating zeism and the maize theory, basing his views on conditions in Italy and Egypt, and W. H. WILSON enlarged on the use of proteins of high biological value in preventing

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recurrences--the amino-acid deficiency theory following the work of United States observers. Thence was evolved the presence of the P.P. factor in vitamin B~ and its deficiency resulting in a " subpellagric state " by E. H. CLEWER in South Africa, amplified later by HARRIETTE CHICK at the Lister Institute, and the Medical Research Council in their special Vitamin Report of 1932. Of all who have studied pellagra and what may be called pellagroid conditions, none has done more to clarify a complicated subject than Dr. HUGH STANNUS, a Fellow of our Society, Lumleian Lecturer of the Royal College of Physicians. I am glad of this opportunity of telling of the painstaking work of one who is known throughout the tropical world and who, I am proud to say, has been a personal friend for 30 years. The list of conditions included under this heading by STANNUS contains many which were discovered, or at least first described, by British medical workers in the tropics. These we can only refer to ; we have not time to describe them in any detail. They are : an outbreak among the prisoners at the Zomba Central Prison, Nyasaland, recorded by STANNUS himself in 1911; epidemic central neuritis recorded in Jamaica and to which OSLER gave the name Scott's palsy ; glossitis and angular stomatitis in Sierra Leone by M. G. BLACKLOCKin 1925 ; A and B avitaminosis, also in Sierra Leone, by E. J. WRIeHT in 1928. Other prison outbreaks were reported by BOASE in Uganda (1928), at Durban by CLEWER (1929) and at Songea District Gaol, Tanganyika (1930). Other conditions included decoquge, described by J. T. BRADLEY, in the Seychelles, in 1929 ; nutritional retro-bulbar neuritis, by D. G. FITZCERALD MOORE, in Nigeria, in 1934 (he has written repeatedly on this subject since that date), kwashiorkor, described by Dr. CICELY WILLIAMS in the Gold Coast in 1935 ; and a similar condition recorded by J. F. CARMAN, in Kenya, in the same year. Sir JOHN MEGAW, in 1936, noted that though cases of pellagra of the typical florid type were few in India, there were nearly 3,000,000 cases of night-blindness. The time at my disposal precludes my telling in detail of several other diseases to the elucidation and treatment of which British workers have made notable contributions. I must rest content with little more than mere references, for in almost every branch of tropical medicine Britons have played a part. Just think how important is the knowledge of the vectors of infection in enabling us to interfere in the spread of disease and then recall Culex and filariasis and the work of MANSON, Aedes and yellow fever (FINLAY), Anopheles and malaria (Ross), Glossina and trypanosomiasis (BRucE and his colleagues), the work of the Sleeping Sickness Commission (BRUCE, A. E. HAMERTON, H. R. BATEMAN, F. P. MACKIE, A. D. FRASER, HALE CARPENTER and LYNDHURST DUKE); of HAMERTON, D. HARVEY and J. B. DAVEY, in the Nyasaland Commission of 1912-14; and that of GuY MARSHALL, C. M. WENYON, STANTON and LEE; and of J. F. CORSON, who, with intrepid courage, carried out experiments on himself in connection with trypanosomiasis, as did A. INGRAM, of Accra, on

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the louse-carriage of relapsing fever in 1924 ; of DUTTON and TODD on Ornithodorus and relapsing fever, on the louse and the same disease in India (CARTER) ; Xenopsylla cheopis and plague (British India Plague Commission). X. astia and plague (HIRST), Aedes and dengue (GRAHAM and CLELAND) and Phlebotomus and Leishmania (HINDLE and PATTON), Planorbis and schistosomiasis and the determination of the two species, Sch. haematobium and Sch. mansoni (LEIPER) and the serological and cutaneous tests for the helminth infestation by FAIRLEY. Again, the naturalistic measures of malaria control are inseparable from the names of K. B. WILLIAMSON, L. W. HACKETT, P. F. RUSSELL, J. W. SCHARFF and SENIOR WHITE. Think of the vast outcome of O. F. H. ATKEY'S findings on cryptic yellow fever--silent areas--in the Anglo-Egyptian Sudan; and let us remember, when we call to mind the enormous developments of prophylactic inoculation against yellow fever, that EDWARD HINDLE was the first to suggest and prepare such a vaccine from the emulsified spleen and liver of infected monkeys, in 1928, and of all that G. M. FINDLAY has done to develop our knowledge of the virus. Let us not omit to do honour to those who died from the diseases they were engaged in investigating--ADRIAN STOKES (1927), W. A. YOUNG (1928), T. B. HAYNE (1930) from yellow fever, and TULLOCH, a member of the Royal Society's Commission on Sleeping Sickness in Uganda. There is hardly any tropical disease to which some material contribution has not been made by a British worker. Thus, when speaking of DAVID BRUCE, we must never forget Lady BRUCE,who gave her husband such loyal and untiring assistance in field and laboratory. She had acquired laboratory technique with KOCH in Berlin, and BRUCE particularly asked that her part in their joint accomplishments should receive due recognition. Death did not part them for long ; they died within 2 days of each other. His work on undulant fever, known in his day as Malta fever, led to his being asked to undertake research into nagana, which he showed to be due to a trypanosome, called later Trypanosoma brucei after him; his later work on trypanosomiasis I need not refer to again. Bruce was President of this Society in 1917-1919. Then we have JOHN EVERETT DUTTON who, during his antimalarial work in the Gambia, found a trypanosome, T. gambiense, in the blood of a sleeping sickness patient. DUTTON died of relapsing fever when carrying out investigations into this disease in the Congo in 1905, at the early age of 31. The spirochaete of Central African relapsing fever was, as you know, named

Spirochaeta duttoni. Another who gained world renown is FINLAY (CARLOS FINLAY) ; we may claim him as British because his father was EDWARDFINLAY, a Scottish physician (his mother was French). In case we are charged with claiming too much, let us compromise by saying that he was half-British and from his clever deductions and suggestions on the transmission of yellow fever by the mosquito, the Tiger mosquito, on which all that followed may be said to have been based, we may justly infer that the half we claim, the Scottish, therefore the British,

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SCp~T

t73

half was the upper half. This has tended to throw into the shade his other contributions such as the solution of the problem of tetanus neonatorum in Cuba and other matters of less note on cholera, leprosy, helminthiasis and ophthalmology. Sir WILLIAM LEISHMANiS, I speak from the standpoint of tropical medicine, chiefly known for his finding of certain bodies in the spleen of a soldier suffering from what was known in 1900 as Dum-dum fever (now kala azar), though he did not record the fact until 1903, when DONOVAN found the same bodies independently ; they are now known, therefore, as Leishman-Donovan bodies. LEISHMANalso did much work at Netley, where I first met him, with Sir ALMROTH WRIGHT, on antityphoid vaccine for troops in the War in South Africa. We have already spoken of Sir PATRICK MANSON and his help to Ross in malaria investigations and research. Whole lectures could be devoted to the pioneer work of this great man ; in fact, whole lectures have been given to it. We all know of his studies on filariasis in China, but he did other things in connection with helminthiasis. He it was who suggested that Chrysops might be the intermediate host of Los los, who confirmed the development of the guinea-worm in Cyclops, and, lastly--perhaps his greatest achievement in promoting the study of tropical medicine--the founding of the London School of Tropical Medicine. Would that time permitted me to tell of the investigations successfully carried out by members of the Colonial Medical Service, of British workers on the Indian Kala Azar Commission, of WENYON, SINTON, MACKIE and NAPIER ; of WHITMORE, STANTONand FLETCHER on melioidosis ; of BASSETTSMITH, HORROCKS, SHAW and JOHNSTONE, of the Royal Society's Commission on Malta Fever and BRUCE'S discovery of the causative organism in 1886; of the work on the same subject by BRUCE, t-IAMERTON, BATEMAN and MACKIE in Uganda in 1910 ; of WIMBERLEY in Northern India in 1907, and BEVAN in Southern Rhodesia in 1921 ; of Sir WILLIAM MACARTHUR and cysticercosis, especially cerebral cysticercosis ; of the studies of a Colonial medical officer in discovering the cause of and the remedy for a disease which had been responsible for thousands of deaths, sometimes 300, occasionally even 500, in a single year in a single West Indian colony, a discovery made after two expeditions sent out from England had returned baffled ; of RAYMOND'S work on the arrow poisons of Africa, but it must not be. One word of warning before I finish ; never let us forget, for it is a healthy check on our arrogance when we think we have conquered a disease, that Nature is no simpleton. HORACE'Swords are as true as ever today:

Naturam expelles furca ; tamen usque recurret. You may think you have won, but She will get back at you somehow when and where you least expect it. She is not going to be subdued by Man, a mere nursling in age, an infant in arms, in comparison with her millions of years'

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experience. Womanlike, she keeps back her best trumps. We thought we had conquered yellow fever when we found the vector Aedes aegypti and the mode of conveyance, but she came back at us with her rural and jungle form, having discarded Aedes aegypti. May I end with a quotation from my Fitzpatrick Lectures of 12 years ago ? " Looking back on the lives of those wh6 have devoted themselves to the study of tropical medicine, we find a few have reaped honours for the work they have done, but many there are who toiled unrecognized.-'Others there be that have no memorial.' Such men labour, often amid squalor and disease, separated from home comforts, from encouragement, from human sympathy and companionship, preserving in silence their lofty ideals, shrinking from publicity, their daily prayer, ' L o r d , give us work and strength to do the work.' But at their deaths, unhonoured and unsung, they gain, may we hope, all the honour, all the reverence paid to the Unknown Warrior, and in the knowledge of duty done, the joys and recompense such as the world cannot give."

Sir HAROLD SCOTT'S paper was followed by two films in colour entitled " Chemotherapy of Experimental Amoebiasis " and " Medical Aspect of Venomous Snakes," shown by Dr. C. J. HACKETT.