Chapter V: Part 5

The chemist Dumas was about this time a member of the French Senate, and in 1865 was charged with the duty of reporting on the petition of some 3,500 ‘propriétaires des Départements séricicoles’ on an epidemic which had for some years been destroying the silkworms of Southern France. Dumas was a native of Alais, a town of the Département Gard, situated in the centre of the silkworm industry, where also the distinguished zoologist Quatrefages was born. Anything that affected Alais affected Dumas; and the epidemic was destroying the prosperity of his native town. The disease was indeed becoming serious. Already in 1849 the silkworms were sickening. The stage at which the symptoms appeared varied--sometimes the eggs were sterile; at other times the silkworms hatched out but to die. If they survived they became shiny; black spots showed themselves; the worms moved with difficulty, refused to eat, and perished; or, if they lived long enough to pupate, the pupa either perished or the moth emerged in an enfeebled state and promptly died.

Efforts had been made to improve the stock by importing eggs from Spain and Portugal, but the Peninsula was soon affected. Eggs were then fetched from Turkey, Greece, and the adjacent islands. These countries too becoming infected, the French cultivators sent further afield and brought eggs from Syria and the Caucasus. Even this resource failed them, and in 1864 every silk-producing country in the world was infected, with the solitary exception of Japan. The loss to commerce was prodigious. In a normal year the value of the cocoons produced in Southern France is, roughly speaking, about £4,000,000; in the years 1863 and 1864 it had fallen below £1,000,000.

When Dumas first asked Pasteur to investigate the disease which was ruining large tracts of the South of France, the latter not unnaturally hesitated. ‘Considérez, je vous prie, que je n’ai jamais touché un ver à soie. Si j’avais une partie de vos connaissances sur le sujet, je n’hésiterais pas,’ he wrote to his friend; but in spite of his hesitation, he left for Alais, and at once commenced a campaign which lasted during the summers of the next five years. Almost immediately on his arrival he detected in the sick silkworms the corpuscles of Cornalia and Filippi, which we now call the _Micrococcus ovatus_. These micrococci are comparatively large and very bright; they occur in the tissues and blood of the silkworm, and are found even in the eggs of the moth. They cause the disease known as Pébrine. The occurrence of the micrococci in the eggs was one of the most important new facts observed by Pasteur. It was the first recorded instance of a parasitic organism being conveyed from one generation to another by the egg; and, although recently the germ of the Texas fever (allied to the malarial organism) has been shown to pass from one brood to another through the egg of the tick which conveys it, it is satisfactory to record that the cases in which this occurs are restricted in number and comparatively rare. The ease with which _Micrococcus ovatus_ could be detected suggested a remedy. A child, when trained, can readily identify the organism. Healthy moths produce sound eggs and healthy larvæ; diseased moths produce diseased progeny. At the present day, throughout the silkworm districts of the South of France, as soon as the moth has deposited her eggs on the piece of linen provided for that purpose, she is pinned up with the cloth; and during the ensuing autumn and winter the women and children are occupied in microscopically examining the body of the moth, crushed in a little water, for traces of the micrococcus. Should any be found, the eggs on the corresponding piece of linen are at once destroyed. Pasteur also showed that the infected stock spread the disease by distributing the micrococci on the mulberry-leaves, whence they enter the silkworm by the mouth; and that the sick inoculate the healthy by crawling over them and piercing the skin with their pointed claws. He therefore emphasized the importance of segregating the sound caterpillars.

The above account conveys no impression of the difficulties under which Pasteur worked. His researches were not only new to himself but to the world. Processes which at the present day are carried out by every medical student had to be devised for the first time. He had to combat the criticism of scientific men, and to overcome the almost invincible ignorance of the agriculturist, an ignorance which at one time advocated the desperate remedy of asperging with absinthe the leaves of the mulberry on which the silkworms fed.

Perhaps Pasteur’s greatest difficulty was the fact that the silkworms did not suffer from Pébrine alone; and it was some time before he recognized that he had to deal, not with one disease, but with two. The second disease, known as the ‘Flacherie,’ is a disease of the digestive system caused by overcrowding and insanitary conditions in the silkworm nurseries. Like Pébrine, it is caused by a micrococcus, _Micrococcus bombycis_. It was whilst investigating this creature that Pasteur discovered that, although the germ itself cannot survive a lengthy period of desiccation, it does in certain circumstances form spores which can survive conditions fatal to the mature organism. This is the first case recorded of a pathogenic organism producing spores, the existence of which has explained so many problems in the spread of disease.

During the period from 1865 to 1870 Pasteur was by no means occupied solely by the silkworm epidemic. In many respects it was a sad epoch in his life. Only nine days after his first arrival at Alais he was summoned to Arbois to see his dying father, but arrived too late. In the autumn of the same year he lost his little daughter Camille, the second who had died. In 1868 he himself was prostrated by a stroke of paralysis, and, although he slowly recovered, it left traces for the remainder of his life.

Few distinguished men of science are left to pursue their investigations undisturbed; and Pasteur was no exception. He had much to do with promoting the publication of the works of Lavoisier, for whose researches he had the profoundest respect. He actively intervened in the elections of the Academy of Science, which appears to consume an infinity of time. He made some preliminary investigations into cholera, an outbreak of which towards the end of the year 1865 carried off 200 victims a day in Paris. He spent a week at Compiègne as the guest of Louis Napoleon, and in a series of _séances_ explained the methods and results of his labours. He wrote on the work of Claude Bernard; he drew up schemes for certain reforms in the University; he gave advice on the higher education of the country, and tried to stem the troubles of the École Normale. In fact, he drew lavishly upon his reserve of health and energy until the breakdown of 1868 was inevitable.

After a tedious recovery he recommenced his work. The success of his methods had been acknowledged by the Austrian Government, who conferred on him in 1868 the prize of 5,000 florins offered to anyone who should succeed in discovering the best means of dealing with Pébrine. The same year the University of Bonn conferred on him the honorary degree of Doctor of Medicine; and in 1869 he was elected a foreign member of the Royal Society. As was to be expected, detractors were not wanting: but these were silenced by the campaign undertaken in 1869 by Pasteur on foreign soil. The Master of the Imperial Household, Marshal Vaillant, who devoted his declining years to scientific experiments, had repeated in his apartments in the Tuileries the observations of Pasteur on the silkworm disease, and had verified the accuracy of his conclusions. He suggested to the Emperor that the Villa Vicentina, a property belonging to the Prince Imperial, should be placed at Pasteur’s disposal for further research. This villa, situated a few miles from Trieste, belonged at one time to the Princess Élise, one of the sisters of Napoleon I., who had lived quietly there after the fall of the First Empire. On her death it passed to her daughter, the Princess Baciocchi, and she in turn bequeathed it to the Prince Imperial. It had been a great centre of the silkworm industry; but for some years no cocoons had been produced, owing to the ravages of the disease.

By short stages, owing to his precarious health, Pasteur made his way to Illyria, taking with him some sound silk-moth eggs, and during the winter not only confirmed his previous researches, but re-established the industry on such a scale that in the following spring the sale of cocoons from this estate alone reached the figure of 26,940 francs. During this winter he dictated to his wife the classic book in which he recorded the results of his last five years’ work. Pasteur returned to Paris through Munich, where he had the pleasure of meeting Liebig, one of the most determined of his adversaries. Although he was unable to induce the German savant to discuss scientific affairs, he always dwelt with pleasure on the courtesy and cordiality with which he was received.

On his return the Emperor nominated him a Senator for life; but, before the gazette appeared in which the nomination would have been recorded, war was declared. From his birth Pasteur had been an ardent patriot, and during the progress of the war he suffered acutely. So much did he feel the reverses of his country, and what he regarded as the undue harshness of the victors, that he felt constrained to return the diploma of Doctor of Medicine which two years before he had accepted from the University of Bonn. He did so in a letter which contained some expressions of feeling with regard to the head of the invading army. These had better have been omitted, but were perhaps pardonable under the circumstances; they in no way excuse the terms of reply which Dr. Naumann, Dean of the Faculty of Medicine at Bonn, permitted himself to use--terms which would be discreditable in an ill-bred street _gamin_.

From 1871 to 1876, the year in which he published his ‘Études sur la Bière,’ Pasteur was again largely occupied with the study of fermentation. Part of his object was undoubtedly to place the French brewers on an equality with the German; and in this he certainly had a large measure of success. To one who knew Paris under the Second Empire and who revisits it under the Third Republic, one of the first changes observable in the life of the _café_ is the enormous consumption of ‘bocks.’ Pasteur’s work, however, went far beyond the establishment of a national industry. He started investigations which have changed brewing from an art into a science; and his most fitting memorial in this respect is the bust which decorates the hall of the Carlsberg Institution at Copenhagen, an institution devoted to the study of all problems of fermentation. In his ‘Études’ Pasteur laid great stress on the fact that every fermentation is brought about by micro-organisms, and he dwells at length on the marked influence which certain bacteria exercise on the nature of the fermentations, and on the character of the beer produced. He did not, however, see, what Hansen demonstrated in 1883, that many of the commonest diseases of beer are caused by certain species of yeast-cell differing specifically from those which cause its normal fermentation. Indeed, he paid but small attention to species, regarding it as waste of time, as it undoubtedly often is, to trouble about names and synonyms.

As Professor Jörgenson and Dr. J. R. Green have shown in two recently-published works, we have learnt much about brewing during the last five-and-twenty years. The nucleus of the yeast-cell has been made visible by appropriate staining; some thirty different species of yeast-cell have been described, and their properties as ferments have been investigated; Buchner, by grinding up the yeast-cells, has produced an extract, called zymase, capable of converting sugar into alcohol; the fact has been established that it is not so much bacteria as other fungi, allied and often congeneric with the yeast-cell, which produce disease in beer; still, allowing a full measure of credit to later workers, we may look back to Pasteur’s researches in the early seventies as establishing for the first time a scientific basis for brewing.

The same remarks are applicable to Pasteur’s work on the diseases due to specific organisms in the region of preventive medicine. We have built and are building a lordly edifice, but he drew the plan and even laid the foundations. More than two centuries ago Robert Boyle--‘the Father of Chemistry and Brother of the Earl of Cork’--had said that he who could solve the nature of fermentations would be without doubt more capable than others of explaining certain phenomena of disease. Towards the end of his ‘Études sur la Bière,’ Pasteur wrote: ‘The ætiology of contagious diseases is on the eve of having unexpected light shed upon it.’ He was already thinking of his investigations into the cause and prevention of contagious disease.

There is a certain malady known, when it attacks cattle and sheep, as ‘charbon’ or ‘sang de rate,’ and when it attacks man, as ‘woolsorter’s disease.’ The term ‘anthrax’ covers the disease in both beast and man; and anthrax is produced by a bacterium known as _Bacillus anthracis_, which had been recognized and was accused of causing the disease before Pasteur began to interest himself in such matters. It annually carried off 20 per cent. of the sheep in the agricultural district of La Beauce, and in Auvergne some 10 to 15 per cent. In certain localities the loss was greater, amounting at times to an annual death-rate of 50 per cent. The disease was by no means confined to France; it was spread over Europe. In the government of Novgorod it was responsible for over 56,000 deaths in three years. In Egypt it was regarded as the direct descendant of the plagues of Pharaoh. It ravaged the large sheep farms of the Argentine Republic.

The bacillus which causes this disease, and which at times by inhalation effects a lodgment in the bodies of those engaged in handling wool and hides, was already known when Pasteur took up the study of pathogenic germs. About the same time it was also attracting the attention of the young German physician Dr. Koch, who subsequently became a severe critic of some of Pasteur’s work; but in this article we are dealing with Pasteur, and limitations of space compel us to leave unnoticed the brilliant work of many investigators who have made the latter end of the nineteenth century one of the greatest epochs in medical history.

Pasteur and his assistants made many fascinating studies on the behaviour and life-history of the _Bacillus anthracis_. He found it very susceptible to slight variations of temperature. The few degrees by which the temperature of a bird’s blood exceeds that of a mammal were sufficient to prove fatal to the bacillus; but by an ingenious experiment he showed that if the temperature of a bird be artificially lowered it becomes susceptible to the disease, though it readily recovers if the artificial surroundings be removed. Pasteur further noted that the bacillus was not equally fatal in all animals, and that it changed its character when passed through the body of certain classes of animals. It was, however, not in studying the _Bacillus anthracis_ that he made the far-reaching discovery of the attenuated virus. This he first noted when at work on chicken cholera, a disease very fatal in poultry-yards; and he made the important discovery by one of those happy accidents which only occur to those who possess the genius for observation. During his numerous experiments he one day chanced to inoculate some fowls with a forgotten culture some weeks old. To his surprise the chickens, though made ill, did not succumb; in fact, they rapidly recovered. He immediately tried what the effect would be if these same fowls were inoculated with fresh cultures of a kind so powerful as to be undoubtedly fatal to a healthy bird which had never suffered from the disease. To his delight, the inoculated fowls resisted the poison, and proved, in fact, immune. This simple experiment is the basis of the world-wide prophylactic measures which are now being carried on against all forms of bacterial disease; and, although Pasteur’s explanation of the weakening of the virus--which he attributed to oxygenation--has been shown to be erroneous, he must still be regarded as the originator of methods for the production of immunity by means of artificially attenuated organisms.

If the virus of chicken-cholera can be attenuated, and when attenuated produces immunity from later attacks, the same is probably true of other germs which can be cultivated outside the body. Arguing in this fashion, Pasteur returned to his study of anthrax. Here he also succeeded, and in the spring of 1881 he demonstrated the value of his treatment. Out of a flock of fifty sheep one-half were inoculated, the other half were not; the whole flock was then infected with the disease. In less than a month the uninoculated were dead of ‘charbon,’ the inoculated were perfectly healthy. The telegram announcing the result to Pasteur, anxiously waiting in his laboratory at Paris, ended with the words ‘Succès épatant!’

So striking a demonstration naturally had a profound effect. It inspired confidence in the treatment. Since the date of this experiment some millions of sheep have been inoculated against anthrax, and several hundred thousand oxen; and it has been calculated that, within the succeeding twelve years, seven million francs were saved by this means alone to French agriculture. Perhaps the convincing nature of Pasteur’s work in this connexion is best shown by the fact that the insurance companies of France insist on inoculation before they will insure sheep and cattle.

We have left ourselves but little space to dwell on the work which occupied the greater part of the last twelve years of Pasteur’s life. Already, in the midst of his work on anthrax, he was thinking of rabies; and in 1881 he proved that it was conveyed through the saliva of the mad dog, and that it could be communicated to rabbits. Saliva, however, was not in every case to be depended on. In some cases it failed to convey the disease. Experiment showed that the poison was concentrated in the brain. To this day no one has succeeded in finding the organism--if it be an organism--which causes rabies. Hence it cannot be cultivated on gelatine in test-tubes, and no modified culture of bacteria can be produced, as is now done in the case of diphtheria and other diseases. Other means had to be devised. After countless experiments it became evident that, if the spinal cord of a hydrophobic rabbit be kept dry at a temperature of 25° C. for a couple of weeks, the strength of the virus has so far vanished that, if an emulsion of the cord be injected, it produces no rabies, but has only a slight vaccinating effect. If two days later an emulsion of a twelve-days-old spinal cord be injected, the vaccinating effect is stronger; but the body, already inured to slight doses of the poison, remains unaffected. Thus, by gradually increasing the strength of the dose, a virus may at length be injected which would infallibly produce rabies but for the previous inoculations. When an animal is bitten by a mad dog, the poison transmitted takes some time to develop--some weeks at least, and often many months. If now the artificially introduced virus ‘gets the start,’ so to speak, of the naturally introduced poison, by the time the latter is at its height the animal has become gradually immunified to the specific poison and suffers little harm. The arsenic-eaters of the Tyrol afford an analogous case. They consume amounts of arsenic which would infallibly produce peripheral neuritis in men unaccustomed to such a diet.

It needed no small courage on Pasteur’s part to inoculate his fellow-creatures against hydrophobia. In 1885 a boy some nine years old, from Meissengott in Alsace, was brought by his mother to the laboratory suffering from fourteen wounds inflicted by a mad dog. After long consultations with his assistants and the most anxious deliberations, he consented to the inoculation of the boy. The next fortnight was a time of intense anxiety, but all went well. His second patient is commemorated by the bronze statue which ornaments the front of the Pasteur Institute in Paris. It represents the struggle between a peasant boy, armed only with his sabot, and a mad dog; the boy was terribly bitten, but the treatment saved his life. It is not easy to arrive at an accurate estimate of the death-rate caused by rabies; but the most careful and moderate estimates show that, before this treatment was in use, some fifteen to twenty out of every hundred persons bitten by mad dogs died a most painful and horrible death. During the fourteen years, from 1885 to 1899, over 23,000 persons known to have been bitten by rabid dogs have been inoculated at the Pasteur Institute; and their average mortality has been 0·4 per cent. In 1899, the latest year for which statistics are available, 1,614 cases were treated, with a mortality of 0·25 per cent. Of these, 1,506 were French and 108 were foreigners. Of the 108 foreigners, 12 came from Great Britain and 62 from British India. It is little short of a national disgrace that we should still be dependent on French aid to succour those amongst us who are so unfortunate as to be bitten by a mad dog; but the nation which gave the use of anæsthetics to the world, and which first showed the value of antiseptics, is largely dependent to-day on foreign aid in dealing with great outbreaks of all sorts of diseases within its borders. The German Koch and the Russian Haffkine are called in to cope with the cholera in India; we fall back upon the Swiss Yersin and the Japanese Kitasato to elucidate the true nature of plague, and to devise methods for combating its ravages. When rinderpest broke out in South Africa it was again to Koch that we turned. The unsatisfactory position of Great Britain in these matters is to some extent due to a small but active section of society whose affection for their lapdogs has overpowered their sense of duty to their neighbours. It is, however, we fear, still more due to the unintelligent treatment of men of science by the Government of the country, and to the want of appreciation of the value of science shown by society at large. If, to balance the list given a few lines above, we recall the work of our countryman Major Ross on the malarial parasite, it serves only to remind us of the difficulties placed in the way of his research by the officials of the service to which he belonged and the slightness of the recognition which for many years he received from the Government.

In 1874 the French National Assembly voted Pasteur, as some recognition of his work on seri-culture, a pension of 12,000 francs a year; nine years later this was increased to 25,000 francs, and it was further agreed that the pension should be continued to his wife and children. In 1881 he was nominated to represent France at the International Medical Congress, which met that year in London. The reception accorded him when, with his host, Sir James Paget, he mounted the platform in St. James’s Hall, overwhelmed him. ‘C’est sans doute le prince de Galles qui arrive,’ he remarked to his host, never dreaming that such acclamations could be meant for him. The following year he succeeded to Littré’s _fauteuil_ at the Academy. In 1888 the President of the Republic opened the Pasteur Institute, which had been erected and endowed by a public subscription from all countries and from all classes; and there in 1892 he received a distinguished collection of scientific men, who had come from all parts of the world to congratulate him on his seventieth birthday.

Three years later his health began rapidly to fail. Two strokes of paralysis followed one another at a short interval, and on September 28, 1895, he died. He lies buried in the Institute he loved so well. A nobler monument, or one more worthy of him who lies therein, has never been erected by man. The benefits which his simple, strenuous, hard-working, noble life conferred on humanity cannot be estimated. They help us, however, to realize the truth of the old Arabian proverb, ‘The ink of science is more precious than the blood of the martyrs.’

M. Vallery-Radot has given what will probably prove to be the definitive Life of Pasteur. He has written at length, and he has written well. That he is not a man of strict scientific training in no way detracts from the merit of the work; rather, in many respects, this makes the book more readable. The pupils of Pasteur, who are now carrying on his work, have, out of the abundance of their knowledge, helped in the more technical portions of the book; whilst M. Vallery-Radot, from his intimacy and relationship with the subject of his biography, has been able to supply those personal details which form so essential and so interesting a part of every good biography.

For one who knew Pasteur only during the last decade of his life to attempt any account of his character may savour of impertinence. Still, it is impossible to close this article without some tribute to his simple dignity of manner, and, above all, to his infinite kindness. No man has done more to lessen suffering in this world, both in man and in the lower animals, and probably but few have felt so much sympathy with suffering in others. As a boy--and French country boys are not more thoughtful about the suffering of animals than those of other races--he refused to go shooting. ‘La vue d’une alouette blessée lui faisait mal.’ As an old man it was a touching sight to see him amongst the sufferers under treatment at the Institut Pasteur, patting the little children on the head, heartening up the timid and giving sous to the brave, infinitely tender to the frightened mothers. ‘Men of science, my Sandra, are always the humanest,’ as Laura said in ‘Vittoria.’ Another dominating trait in his character was his unflinching desire for truth; to ‘prove all things,’ and to ‘hold fast that which is good,’ was the motto of his working life. His success was in no small measure due to the rigorous tests he applied at all stages of his investigations; it was also due to the untiring assiduity with which he worked, never sparing himself, never in any way thinking of himself. But, above all, it was due to the intense thought he bestowed upon his researches. Concentrating his intellect upon the problem in question, he thought out all possible solutions, and was prepared for all possible eventualities. It was this power of thought, coupled with a matchless gift of observation and experiment, that enabled him to leave a name which cannot be forgotten whilst civilization endures.

MALARIA

_There in a wailful choir the small gnats mourn_
_Among the river sallows, borne aloft_
_Or sinking as the light wind lives or dies._
JOHN KEATS: ‘To Autumn.’

It has been said that one-half the mortality of the human race is due to malaria. This may very well be an exaggeration, but there can be little doubt that, of all the ills that flesh is heir to, malaria is the most deadly, and exercises the most profound influence on the distribution and activities of man. It will be seen later that the disease is most rife where the densest populations are found, and the mortality of such a closely crowded area as India gives some idea of the enormous loss of life and the widespread suffering caused by this disease. In 1892, out of a total population in India of 217,255,655, the deaths from all causes reached the figure of 6,980,785. Of these, 4,921,583 were ascribed to ‘fever.’ All these fevers were not, of course, malarial, but comparison with other statistics leads to the belief that a high percentage of them was caused by malaria. Major Ross states that in 1897 over 5,000,000 deaths in the same country were recorded as due to ‘fever,’ and that out of a total strength of 178,197 men in the British army in India, 75,821 were treated in the hospitals for malaria. Fifty years ago the loss from malaria amongst the European population of India was 13 per thousand. With improved methods of living and more skilful treatment this has been reduced to 7 per thousand; but the native, who is slow to change his ways, and usually averse to modern methods of treatment, still retains a very high fever death-rate--over 18 per thousand. During the years 1887-1897 the average mortality in Italy attributed to malaria was 15,000 a year, and 2,000,000 patients annually suffered from ‘fever.’

Apart from the mortality due to this disease, the amount of suffering and the decline in human power and activity which it entails deserve careful attention. Compared with the number of patients, the number of deaths is by no means large. In round numbers, out of every thousand soldiers in the British army in India in 1897, 420 men were attacked by malaria, but only one in a thousand died; even in the ‘most malarious’ districts the death-rate only amounted to 6 per thousand. In Sierra Leone, a district much more fatal than any in India, the average death-rate of the white troops, based on hospital records extending from 1892 to 1898, is estimated by Major L. M. Wilson at 42·9 per thousand, whilst that of the coloured troops is 5·9 per thousand. On the other hand, the European troops show an annual number of cases of 2,134 per thousand, and the non-European troops one of 1,056 per thousand. These figures probably under-estimate the amount of fever amongst the troops. It must be remembered that many soldiers who have slight attacks of fever do not present themselves at the hospital, whilst of those who do a considerable number are only detained for slight treatment, and are never entered on the hospital books, and so are not recorded on the returns.

From the statistics quoted above, it appears that of our soldiers in India three out of every seven suffer from an annual attack of malaria sufficiently pronounced to be recorded on the medical books, whilst our soldiers on the west coast of Africa have an average of at least two attacks a year, and a considerable number of them die. There is no reason to believe that the civil population of India or West Africa is in any degree more exempt from the disease than the military, but the statistics in the latter case are more readily accessible.

Malarial fever, when it does not kill, leaves great weakness behind; and all who have watched malaria patients, or patients who are already recovering from an attack, cannot fail to have noticed the listlessness and want of interest in their surroundings and the lack of inclination to work that they all show. Apart from the mortality, the disease probably levies a heavier tribute on the capacity of the officers and officials who administer the British Empire than does any other single agency.

Before describing the organism which causes all this misery a word or two must be said about the distribution of the disease. Roughly speaking, malaria is confined to a broad irregular belt running round the world between the 4th isothermal line north of the Equator and the 16th line south. It is, however, said to occur occasionally outside these limits--for instance, in Southern Greenland and at Irkutsk in Siberia; but until recently the accurate diagnosis of the disease has been difficult, and too much reliance must not be placed on these statements. The chief endemic foci of the disease are along the banks and deltas of large rivers, on low coasts, and around inland lakes and marshes. Malaria is common all round the Mediterranean region: it was well known to, and its symptoms were clearly noted by, the early physicians since the time of Hippocrates. They even recognized the difference between the mild spring and summer attacks and the more pernicious effects of the autumnal fever. In France there are several prominent malarial districts: the valley of the Loire and its tributary the Indre, and the valley of the Rhone; also the sea-coast stretching from the mouth of the Loire to the Pyrenees, and again the Mediterranean sea-board. It occurs in Switzerland, and is found in Germany along the Baltic coasts, and on the banks of the Rhine, the Elbe, and other rivers, and in many other parts. Scarcely a province in Holland is quite free from it, and it is found in Belgium and around Lake Wener, in Sweden. It extends along the Lower Danube and around the Black Sea, and spreads across Russia, being especially prevalent along the course of the Volga and around the Caspian. From Europe it spreads over Asia Minor, and affects all Southern Asia as far as the East Indies, but in Japan it is curiously rare. It is also infrequent in Australia--where it is confined to the northern half of the continent--and in many of the Pacific Islands; and it is unknown in the Sandwich Islands, New Zealand, Tasmania, and Samoa. In America it is more common, and of a more severe type an the Atlantic sea-board than on the Pacific; in the last hundred years its northern limit is said to have retreated in the centre of the continent, though some observers think it is creeping further north in the Eastern States. In a mild form it is known around the Great Lakes, and in Canada and in New England; but it reaches a high degree of intensity in the Southern States, Mexico, Cuba, and Central America, where it probably played a greater part in ruining the projected Panama Canal than all the corrupt financing of the speculators in Paris. It extends throughout the warmer parts of South America, and is known in a virulent form all over Africa except the extreme south.

In Great Britain it used to flourish. The following extract from Graham’s ‘Social Life of Scotland in the Eighteenth Century’ shows what a part it played in the life of the Scottish peasant:

‘The one ailment to which they were most liable, and in which dirt
had no share, was ague. This was due to the undrained land, which
retained wet like a sponge, and was full of swamps and bogs and
morasses in which “green grew the rushes.” Terribly prevalent and
harassing this malady proved to the rural classes, for every year a
vast proportion of the people were prostrated by it, so that it was
often extremely difficult to get the necessary work of the fields
performed in many districts. In localities like the Carse of
Gowrie, which in those days abounded in morasses and deep pools,
amongst whose rushes the lapwings had their haunt, the whole
population was every year stricken more or less with the trouble,
until the days came when drainage dried the soil, and ague and
lapwings disappeared.’

In England it was once very prevalent. James I. died of ‘a tertian ague’ at Theobalds, near London, and Cromwell succumbed at Whitehall to a ‘bastard tertian ague’ in 1658, a year in which malaria was very widely spread and very malignant; and it is only within recent memory that the fen districts in Cambridgeshire and Lincolnshire, Romney Marsh in Kent, and the marshy districts of Somerset, have lost their evil reputation for ague. The older chemists in the towns in the fen districts still recall the lucrative trade their fathers carried on in opium and preparations of quinine with the fenmen during the first half of last century; but with the improved drainage of the fens this has all disappeared, and at present cases of endemic malaria appear to be unknown in England, though sporadic cases turn up at rare intervals. It was also very prevalent along the estuary of the Thames, both on the Essex and Kentish marshes. Pip in ‘Great Expectations’ says to his convict:

’“I think you have got the ague.” “I’m much of your opinion, boy,”
said he. “It’s bad about here,” I told him. “You’ve been lying out
on the meshes, and they’re dreadful aguish.”’

Ireland, which appears at first sight peculiarly adapted for the disease, seems to have been remarkably free from it. It may be that the strong antiseptic quality of the peaty bog-water hinders the development of the larval mosquito.

Turning now to the cause of the disease, it is interesting to note that the discovery of the organism which produces all this misery and death took place just about the time when Koch was making his far-reaching investigations into the cause of tuberculosis. In 1880 Koch was at work on the tubercle bacillus; and in the same year a French army surgeon, named Laveran, looking down a microscope in a remote military station in Algiers at a preparation of blood taken from a malarious soldier, recognized for the first time the small organism which has played a larger part in human affairs than the greatest politician or general that ever lived. This small organism is an animal, not a plant. It belongs to the great group of single-celled organisms, mostly microscopic in size, called Protozoa, and it lives as a parasite inside the body of other animals, from which it abstracts what nutriment it needs. Before describing its structure and life-history, a word or two must be said about its surroundings in the body of man.

That blood consists of a fluid in which enormous numbers of cells called blood-corpuscles float is now a matter of common knowledge. These corpuscles are of two main kinds, the red and the white, but the red surpass the white in number, in proportions ranging from 300 up to 700 to 1. A cubic millimetre of blood contains about 5,000,000 red corpuscles; and since these act as the carriers of oxygen from the lungs to the tissues all over the body, and on their return journey carry away the carbon dioxide from the tissues to the lungs, where it is given off, it is obvious that the presence of a parasite in the red corpuscle will have a most serious effect upon the welfare of the body.

Before Laveran’s discovery, Lankester had described a parasitic organism living in the blood-cells of a frog, and within the last twenty years numerous other organisms have been discovered and described by various investigators living in the blood-corpuscles of reptiles, birds, monkeys, and bats. There are at least three species of Hæmatozoa, as they are called, which live in the blood of man, and these three correspond to the three kinds of malaria--the tertian, the quartan, and the æstivo-autumnal, or, as it is often termed, the irregular type of malarial fever, which occurs so frequently in the late summer and autumn in Italy and elsewhere. The hæmatozoön causing the last-named fever has been especially studied by the Italian observers, and it differs more markedly from those causing the tertian and quartan fevers than the latter do _inter se_. It is not universally conceded that the differences between these three forms of organism are such as to establish a difference of species, but the weight of opinion is in favour of this view. Ross even places the parasite of the æstivo-autumnal fever in a separate genus, and we have throughout this article adopted his nomenclature. Zoologically he groups all the three species infesting man in Wassielevski’s family Hæmamœbidæ, which, besides the human parasites, includes a species found in monkeys, three species in bats, and two in birds. The species causing tertian and quartan fevers are grouped by Ross in the genus _Hæmamœba_, the former being called _Hæmamœba vivax_, the latter _Hæmamœba malariæ_. The parasite causing the æstivo-autumnal fever is called _Hæmomenas præcox_.

With the exception of a few details the life-history of all these forms is practically identical, although the time which is occupied by different phases of their life-cycle varies in the different species. The account given here applies in the main to them all.

The organism which Laveran saw living in the blood-corpuscles of his malarious patient was a minute cell of irregular shape whose nucleus can be demonstrated by the use of appropriate reagents. The cell constantly but slowly changes its outline, pushing out and withdrawing blunt rounded processes; in fact, the cell resembles the lobate forms of one of the simplest microscopic animals we know, the Amœba (Fig. 1). The movements and change of shape consequent on them are termed amœboid, and the organism in this stage is known as an amœbula. These amœbulæ whilst in the blood-cell grow rapidly, and in some way they collect the hæmoglobin, or colouring matter of the red corpuscle, within their own bodies, and convert it into a number of dark brown or black pigment granules, which crowd around the nucleus of the parasite. This pigment, the so-called malarial pigment or melanin, had been recognized by Virchow and others about the middle of the nineteenth century as a characteristic product in the blood of malarial patients. The amœbulæ continue to grow rapidly, at the expense of their cell-host, until, after a definite period, which varies from one to several days, they become mature, and by this time they have completely filled up the red corpuscle, whose scanty remains form a tight skin round the fully-grown parasite (Fig. 1, 1-8). When mature, one of two things happens--either they become (1) gametocytes, whose meaning and fate we will consider later, or they become (2) sporocytes. In the latter case the nucleus of the amœbula breaks up into a number of small nuclei, and each surrounds itself by a small mass of protoplasm and forms a spore (Fig. 1, 5-8). The result of this process of division may be roughly realized if we imagine an orange with

Nos. 1, 2, 3, 4, show the growth and the changing shape of the
parasite within the blood-corpuscle; Nos. 3, 4, etc., show the
aggregation of the pigment, melanin, in the parasite; No. 5 is a
sporocyte, which in Nos. 6, 7, and 8, shows the several stages of
sporulation; No. 9 shows the spores derived from a single
sporocyte, escaped from the blood-corpuscle and free in the
blood-plasm, ready to infect new corpuscles; No. 10 is a male
gametocyte, removed from the body of man, and either in the stomach
of _Anopheles_ or on a microscope-slide, forming there flagella or
spermatozoa, _a_, Parasite; _b_, red blood-corpuscle; _c_, spore;
_d_, granules of pigment, melanin; _e_, flagellum or spermatozoön.
(From Thayer.)
]

FIG. 2.--VARIOUS STAGES WHICH THE PARASITE OF THE ÆSTIVO-AUTUMNAL
FEVER, HÆMOMENAS PRÆCOX (ROSS), PASSES THROUGH IN THE BODY OF THE
MOSQUITO ANOPHELES. MAGNIFIED 2,000 TIMES. AFTER ROSS AND
FIELDING-OULD.

No. 1, Flagella or spermatozoa from male gametocyte (see Fig. 1
above); No. 2, flagellum or spermatozoön entering and fertilizing
the female gametocyte; No. 3, the fertilized cell or zygote; Nos.
1, 2, 3, are found in the blood in the stomach of the _Anopheles_;
No. 4, the fertilized cell piercing the wall of the stomach of the
mosquito to come to rest at No. 5, between the epithelial lining of
the stomach and the muscular sheath.

_To face page 136._]

but one pip in each quarter. Then the skin of the orange will represent what is left of the red blood-corpuscle, the flesh will represent the divided sporocyte, each quarter will represent a spore, and the pip will represent its nucleus.

At this stage the skin to which the red corpuscle has been reduced breaks, and the spores fall into the liquid part of the blood (Fig. 1, 9). The pigment granules which escape at the same time also pass into the liquid of the blood, and are eaten up and removed by those scavengers of the vascular system, the white corpuscles. Each of the spores, after remaining a short time in the fluid of the blood, attaches itself to a new red corpuscle, penetrates its body, and becomes a small amœbula, which repeats the life-history described above. In this way a few organisms will soon produce enough spores to infect a very large number of blood-corpuscles; as many as 60 per cent. are in some cases infected. The severity of the attack naturally depends in a great degree on the number of corpuscles infected. Laveran not only first recognized and described the organism[4] we are dealing with, but he definitely connected its presence with malaria; but it was not until some time later, in 1885, that Golgi described the sporulation of the sporocyte and pointed out that the moment of the escape of the spores from the red corpuscle coincides with the paroxysm of the fever. Since all the amœbulæ of one crop are at about the same stage of growth in any one host, millions of spores in a well-infected patient are thrown into the liquid of the blood at about the same time; and it is clear that this must be accompanied by a profound disturbance of the system. This disturbance manifests itself in a feverish attack. The period when the spores have left the corpuscles and are free in the liquid of the blood is also the time at which the administration of quinine is said to be most effective. Further, it is only at this stage that the disease can be artificially transferred from one man to another. All efforts to transmit the gametocytes have ended in failure.

_Hæmamœba vivax_, which causes the tertian fever, passes through the various stages of its life-history in man in forty-eight hours; hence the febrile paroxysm occurs every second day. Malaria is usually of the tertian type, and this is certainly the most common form in temperate climates. Occasionally the infection has been repeated, and we may find that there are two groups of the parasite present in the blood, which arrive at the sporulating stage on alternate days; in this case the febrile symptoms manifest themselves every day, and the type of malaria is designated ‘quotidian intermittent fever.’ In this case, if a single dose of quinine be administered at the right time, one group of parasites is killed off and the quotidian fever is reduced to a tertian. There may occasionally be more than two groups present, or the parasites may for some reason have failed to arrange themselves in groups, in which case the fever becomes irregular or continuous.

In the quartan fever the parasite _Hæmamœba malariæ_ takes seventy-two hours to complete its cycle in man, and the paroxysms occur every three days--that is, there are two days without febrile symptoms, followed by a day when there is a paroxysm. This form is common in Sicily and in certain parts of Italy--for instance, around Pavia. Just as in the tertian fever, so in quartan there may be a second infection, in which case paroxysms arise on two successive days, followed by a day of intermission of the fever. If a third group be present, we have a quotidian fever. The æstivo-autumnal fever, due to _Hæmomenas præcox_, is noted by a marked irregularity in its clinical symptoms. It usually sets in during August, September, or October, and is attended by much more serious results than are the regular intermittent fevers. The pernicious or malignant form of malaria, rarely seen in temperate climates, but common in the tropics, is caused--in many cases, though perhaps not in all--by the same parasite.

From what has been above described, it is evident that when once the parasite has obtained entrance to the blood it may remain and multiply for years. The parasite is, however, very susceptible to the poisonous action of quinine, and this is especially the case at the time when sporulation has just taken place and the spores are being set free in the blood. Quinine seems to have little or no effect on the organisms whilst they are inside the blood-corpuscle, but shortly before the paroxysm is due it should be administered. Quinine is amongst the very few absolutely trustworthy specifics known to medical science. It seems to have been introduced into Europe in the year 1640 by the Countess of Chinchon, a small town south-east of Madrid. The Countess was Vice-Queen of Peru, and in 1638 was cured of a tertian fever by the use of Peruvian bark. Shortly afterwards she started for Europe with a supply of the drug, but unfortunately died on the voyage. About a hundred years later Linnæus named the plant after this lady, but acting on erroneous information omitted the first ‘h’ in the name, and called the plant Cinchona. According to some authorities the word ‘quinine’ is derived from ‘quina,’ the Spanish spelling of the Peruvian word ‘kina,’ which signified bark.

But to come back to the parasite. It was mentioned above that the amœbulæ become either sporocytes or gametocytes. We have followed the fate of the former and must now turn our attention to the latter. In the genus _Hæmamœba_ the gametocyte has a general resemblance to the sporocyte before its nucleus divides and it begins to form spores; and it is impossible to predict which amœbulæ will become sporocytes and which will become gametocytes. In _Hæmomenas_, however, the gametocyte can be recognized at an early stage. In this genus some of the amœbulæ become globular and ultimately form spores, whilst others become elongated and slightly curved; in fact, they assume the shape of minute sausages. These are the gametocytes. It is on this difference in shape that Ross has founded his new genus for the parasite of the æstivo-autumnal fever, all the essential characters of which had, however, been previously recognized by Italian and American observers.

So long as the gametocytes remain in the blood of the patient they undergo no further development; on being liberated from the cell into the fluid of the blood, they degenerate and die; but if they be removed, even only on to a microscope-slide, they begin to develop. They escape from the red corpuscle in which they have hitherto been confined, and some of them--the male gametocytes--are then seen suddenly to emit long filaments (Fig. 1, 10). These filaments can be watched under a high power struggling violently to free themselves from the cell which has given rise to them. Ultimately they succeed, and breaking loose, at once dart away amongst the corpuscles and other debris on the slide. So long ago as 1880 Laveran had seen these bodies, but until 1897 their nature was quite misunderstood. This formation of the filaments or flagella, sometimes called ‘flagellation,’ can only take place at comparatively high temperatures. This has an important relation to the seasonal variation in the prevalence of the disease.

Hitherto in this article we have only studied the malarial parasite inside the body, with the exception that we have just seen that, should it get out, certain cells undergo a further development and produce mobile filaments. It occurred to many that these filaments might be spores, which were in some way carried into the blood of man. Later research showed that this is not their true meaning; but, acting on some such belief, Dr. Patrick Manson propounded the hypothesis that the spores may be conveyed to man by the intervention of some blood-sucking insect; and the brilliant and laborious researches of Major Ross, undertaken with the view of establishing the truth or falsehood of this hypothesis, have within the last few years cleared up the whole question of the transmission of the disease from one patient to another.

It is a well-established belief in many malarious countries that the mosquito plays a part in the infection. The negroes of the Usambara Mountains, who acquire the disease when they descend to the plains, even use the same word to denote the disease and the mosquito. In Assam, in Italy, and in Southern Tyrol, the belief in the mosquito origin of malaria obtains. Experienced travellers, like Livingstone, Emin Pasha, and General Gordon, insisted on the importance of mosquito-nets, thinking that the netting ‘acted as a filter against the malarial poison,’ and knowing by experience that its presence diminished the tendency to the disease. The whole epidemiological evidence was put together in a masterly essay on the mosquito theory, read before the Philosophical Society of Washington in 1883, by Professor A. F. A. King. There was thus a considerable body of opinion in favour of the mosquito-malaria theory, when, in 1894, Manson explained his views to Major Ross, at that time a surgeon in the Indian Medical Service.