No. 4440.

OCTOBER 3, 1908.

The Hurley LectureON

RECENT ADVANCES IN SCIENCE AND THEIRBEARING ON MEDICINE AND

SURGERY.Delivered at Charing Cross Hospital on Oct. 1st, 1908,

BY SIR PATRICK MANSON, M.D. ABERD.,F.R.C.P. LOND., K.C.M.G., F.R.S.,

LECTURER ON TROPICAL DISEASES AT ST. GEORGE’S HOSPITAL ANDCHARING CROSS HOSPITAL MEDICAL SCHOOLS AND AT

THE LONDON SCHOOL OF TROPICALMEDICINE.

MR. PRESIDENT AND GENTLEMEN,-In preparing the fol- I

lowing remarks I have assumed that the council of Charing f

Cross Hospital Medical School have asked me to deliver this sthe seventh biennial Huxley lecture because they are im- 1

pressed by the position attained by tropical medicine inrecent years and because they know I have given someattention to the subject. I appreciate and am grateful forthe compliment implied, although I fear I can do only scantjustice in the short time at my disposal to what has becomea large and important subject.

All must recognise that tropical medicine is a theme

specially appropriate for a Huxley lecture, seeing that

tropical medicine, so far as the etiology and prophylaxis oftropical disease are concerned, is in great measure a branchor development of one of those sciences so intimately asso-ciated with Huxley’s name-natural history. Moreover, thesuccess with which the study of tropical medicine has beenattended is in great measure due to the employment of thosemethods of investigation and teaching so consistentlyand powerfully employed by that great master of natural

science-namely, clearing the mind of tradition and cant,careful observation of facts, hypotheses based on fact, test-ing such hypotheses by experiment and by their consistencywith other facts, and finally, if verified, the fearless applica-tion of the proved hypothesis in practice.Some of you may recollect the opposition encountered

by those of us who 10 or 12 years ago were endeavouring tomake the study and teaching of tropical medicine a distinctdepartment of medicine. That opposition has, I believe,subsided if not ceased altogether, for it is now generallyrecognised that this subdivision of medicine is a natural oneand one practically necessary, one founded on a well-established principle. That principle, briefly stated, is this-namely, that the possible range of a geographically limiteddisease depends, not on the influence of climate or localityon the human body or on germs already established in thehuman body, but as they influence the disease germ itself inand during its passage from one human host to anotherhuman host-that is to say, on the disease germ while it isoutside the human body. If as regards any given diseasegerm the climatic and local conditions in any given countryare unfavourable to the germ while it is outside the human

body, the germ may be imported time after time, but thedisease it is responsible for will not spread or becomeestablished as an endemic. On the other hand, if the localand climatic conditions are favourable to the germ while out-side the human body, once the germ is introduced, given theopportunity, the disease it is responsible for will surelJspread.

It so happens that certain germs require for their successfulpassage from host to host a high atmospheric temperatureor they require animal intermediaries which flourish only ir

high atmospheric temperatures. These conditions beinexistent only in tropical or subtropical countries, or i)

temperate countries during the summer season, the diseaseproduced by the germs referred to can originate and spreacin warm countries or seasons only. Malarial disease and it

germs are, perhaps, the most familiar example of thiprinciple. Malarial disease is caused by a protozoal organisIwhich in man lives in the red blood corpuscles. Under norm!conditions the germ is powerless to leave its human host cto enter another human host. To effect this necessary transl1tion it requires an insect intermediary-a particular kind (

No. 4440.

)squito. This mosquito for its well-being, amongst otherings, demands a high atmospheric temperature ; thereforeis insect flourishes in warm climates or in the warm

a,son of temperate climates. Hence human malaria is asease special to warm climates-that is to say, a tropicalsease.

Besides malaria, I could adduce both from human and fromaerinary pathology many additional illustrations of this

’inciple. For example, yellow fever, African tick fever,ypanosomiasis, filariasis, certain kinds of spirochuctiasis,id so on. In all of these an animal intermediary of tropicalhabit is necessary for the transmission of the germ and there-)re of the disease.There are other tropical diseases for the spread of whicho such living intermediary is necessary ; nevertheless, hightmospheric temperatures being required by their germs inaeir passage from host to host, these diseases are properlylassified as tropical. In their case the germs require afarm medium in which to accomplish necessary develop-mental changes which, when complete, qualify the germ toffect successfully a lodgment in the human host. Ankylo-tomiasis is an example of this. If when it leaves the humaniost the egg of the ankylostome does not quickly meet withb warm moist nidus it perishes ; if it meets with such a nidus,he larva is hatched out and, opportunity serving, enters alew human host, and so the disease it gives rise to is spread.

It is this necessity on the part of the germ for either ajropical intermediary or for a warm medium, such as occuraaturally only in tropical countries, that constitutes themain determining factor in the geographical distribution andLimitation of tropical disease and which, so to speak,specialises the subject. This is the reason for, and the

justification for, specialising the teaching and study of thesubject, and this it is that determines the lines on which

tropical medicine has to be studied and taught.What might be described as a corollary pendant to the

general principle that the intermediary or medium requiredby the disease germ is the agent that principally deter-mines the distribution of tropical disease imposes welcomelimitations to the field of study. The principal tropicaldiseases (I do not include in this the skin and thefood diseases) are caused either by protozoa or byhelminths. So far as we accurately know, none of thesedisease germs are bacterial. The reason for this fact, whichpathologists are only beginning to appreciate, lies in thecircumstance that the pathogenic bacteria are not materiallyaffected, so far as their viability and transmission are con-cerned, by ordinary atmospheric temperature ; neither dothey require to undergo developmental changes outside thehuman body before they can enter another human body, and,therefore, although they may be favoured or the reverse bysuch, they are not absolutely dependent on any animal orother geographically limited medium. Several bacterialdiseases which are often classed as tropical-for examplecholera, certain kinds of dysentery, leprosy, plague, Medi-terranean fever, &c., are not really tropical. Experiencehas shown that these diseases can flourish in anyclimate. It is only because those hygienic and socialconditions most favourable to their spread are met withat the present day in greatest perfection in the tropics, thatthey are conventionally regarded as tropical; they have nomore real claim to be regarded as tropical than tuberculosisor syphilis has. In times past, and even at the present day,they were or are common enough in some places or condi-tions in temperate or even in cold countries.Thus in the study of tropical disease bacteriology may be

relegated to quite a secondary place. The student’s atten-tion is confined almost entirely to protozoa and helminths, tothe special vectors or media of these organisms, to theirpathological effects, and to the prophylaxis and treatment of

. the diseases they give rise to.; I might mention in passing that those who plan schools ori courses for the teaching of tropical medicine should recognisei this large element of natural history in the subject and thatl if possible they should include in the teaching staff (1) a9 protozoologist, (2) a helminthologist, and (3) an arthropo-idologist (I say arthropodologist because the known inter-imediaries of the pathogenic protozoa and helminths are1 nearly all of them either insects, ticks, or crustaceans) inr addition to the usual pathologist, systematic clinical and.- hygiene lecturers having at their disposal a suitable hospitalt with a tropical clientue, besides a laboratory, museum, and

992

library. Such machinery I regard as essential for theefficient teaching of tropical medicine. It is towards this

position of theoretically indicated efficiency that those of us’Who have been working for the London School of TropicalMedicine for the last ten years have been struggling, andto which, I am glad to be able to say, we have at lastattained.

I have prepared a list of the principal tropical diseaseswith, so far as we know them, their germ causes and inter-mediaries. These tables (Tables I., II., and III.) indicatein synoptical fashion the leading facts in our presentknowledge of the subject, and the many gaps that remainto be filled in. You can see from them how completely theprinciple I have enunciated as regulating in the mainthe distribution of tropical disease is substantiated. Thetables also show well how much has been accomplishedin recent years. If we regard, as I think we may, thisrecent progress as an earnest of what will be accom-

plished in the near future, it leads one to anticipate thatwithin a very short period all the gaps in these tables willbe filled in, and new diseases, new disease germs, and newand more reliable methods of diagnosis, prevention, and

possibly of treatment be discovered.In a Huxley lecture the discussion of a biological

subject cannot be regarded as inappropriate, even if that

subject implies a large amount of what in the presentstate of knowledge is necessarily of a highly speculativecharacter. Huxley loved a biological problem. Hewas a great collector of facts, it is true-a greatobserver; but he tells us his interest in facts was I

chiefly in as far as they illustrated and led up to

principles. In his search for and contemplation of facts,i in his endeavour to arrive at principles, he recognised andinsisted on the value of hypothesis. In his day, as at thepresent day, it was the fashion with some to decry and scoffat any hypothesis, however reasonable, that might be

advanced in an attempt at explaining or coordinatingfacts. According to such people the only thing worthy

the name of science is fact. Huxley, however, was not ofthis way of thinking. He held that in science hypothesis, had a distinct and honourable place, that it was of the

greatest value in stimulating and guiding observation and inbringing about discovery. Witness his strenuous advocacyof Darwinism, an advocacy so fully justified by result.

Huxley, however, was ever careful to distinguish betweenhypothesis and fact, and it is in this spirit that I wouldbring before you some biological problems having importantbearings on tropical pathology and possibly on phases ofpathology other than tropical, and, also, certain hypotheseswhich may or may not be verified in the future, but whichcertainly suggest lines of work which, if pursued, could notfail to elicit new and important facts and perhaps sounderexplanations than those I propose to offer.

In the largest and most important section of tropicaldiseases the germs (I shall take that of malaria as an

example) are carried, as I have explained, from human hostto human host by animal intermediaries, in this instance ananopheline mosquito. But the malaria mosquito does notfunction merely as a simple mechanical vector, in the waythat the physician’s lan,cet does when it transfers the vaccinia

TABLES OF TROPICAL DISEASES SHOWING OUR PRESENT KNOWLEDGE OF THEIR ETIOLOGY AND MEANS OFPROPAGATION.

TABLE I.--Diseases Ilue to Ye.qetable Parasites.

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TABLES OF TROPICAL DISEASES SHOWING OUR PRESENT KNOWLEDGE OF THEIR ETIOLOGY AND MEANS OFPROPAGATION C<7HMK<.’).

TABLE IL-1?iscases D1w to Animal Parasites.

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TABLES OF TROPICAL DISEASES SHOWING OUR PRESENT KNOWLEDGE OF THEIR ETIOLOGY AND MEANS OFPROPAGATION ("6’OKMC.

TABLE II.-Diseases Due to Ammal Parasites (continued).

TABLE lII.-Diseases of Unknomn Etiol,ogy.

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germ from arm to arm. The mosquito not only conveys themalaria germ but it also serves as a medium in which that n

germ undergoes certain developmental changes necessary for 11its existence as a species, as well as for its successful intro- eduction into a fresh human host. These changes are of a o

sexual nature and include impregnation of the female malaria h

germ by the male malaria germ, and result in the develop- e

ment of a multitude of young malaria germs which, should a

they chance on the opportunity of being introduced into human E

blood by their mosquito nurse and vector when she again bites r

a human victim, live and multiply, generation following i

generation for any time up to two or three years. Until the i

developmental changes occurring in the mosquito, changes 1which take some ten days to effect, are completed themosquito may bite but she will not infect. The same I

principle holds good in the case of those other animal-intermediary-using protozoal germs whose life-histories have e

been worked out, and we are justified by analogy in con-jecturing that they also apply to many similar protozoalgerms whose life-histories have as yet not been fullyascertained.

In a word, certain blood-haunting protozoa requiring aninsect or other arthropod vector make use of that vector asa medium for sexual development. May we regard this as ageneral law applicable to all such blood-haunting protozoa ? 7

Unfortunately, there are certain of these pathogenicprotozoa in respect to which, notwithstanding their employ-ment of an insect or other arthropod vector, careful researchby highly trained and competent investigators has failed todemonstrate convincingly sexual changes within their

respective vectors. The trypanosomes, now known to be alarge and important class of pathogenic protozoa, are

notorious examples of this. An indubitable sexual stage ofthe germ of sleeping sickness, Zrypanosomcc gambiense, themost important of these, has not hitherto been clearlydemonstrated in its vector, the tsetse fly, 6*MMM palpalis.

I shall endeavour to examine the case as regards thissleeping sickness trypanosome, for, depend upon it, if thelaw I have formulated applies to this trypanosome, or anytrypanosome for that matter, it applies to all trypanosomes ;if it does not apply to this trypanosome it does not apply toany trypanosome. If there be such a law it is of the utmost

practical importance that we should not merely suspect itsexistence but that we should be sure of it. The subject isof more than theoretical interest. Accurate knowledge isthe true and proper basis of practical medicine, especiallyof preventive medicine. Witness what it has done for the

prevention of malaria and yellow fever. Half knowledgemeans half-hearted measures ; full knowledge means hope-fulness in endeavour, precision in directing, and economy incarrying out.

I propose to deal with the arguments both for and againstthis what I might designate hypothetical law, taking, as Ihave said, the sleeping sickness trypanosome as a text. Ishall allude, though very briefly, to the arguments in favourof the law, more fully to those against it.As regards the former, a principal argument is based on

analogy. I am fully aware that this method of reasoningmust not be carried too far. It has a certain value, however : iin the present instance it is distinctly favourable.There can no longer be any doubt that the trypanosome oi

sleeping sickness is conveyed principally, although perhaplnot exclusively, by the tsetse fly, Glossina palpalis. Direcexperiment-the correspondence of the topical as well as othe regional distribution of the fly and of the disease-practically proves this. If the fly acts merely as a mechanicavector of the trypanosome, why is the trypanosome not conveyed more frequently than is the case by other bitinginsects, such as mosquitoes, fleas, bugs, tabanidse, &c., an’

therefore to be found along with its disease, sleeping sic&Egrave;ness, not merely, as is the case, on the banks of Africarivers and on the shores of African lakes, but everywherwhere man-biting insects occur ? 7 You can vaccinate withlancet, a needle, or even with a thorn; in fact, with an]thing that will scratch. Surely this predilection of the trepan<some for Glossina palpalis must be that Glossina pal palis not merely mechanically serviceable to the trypanosonbut physiologically necessary. What more probable th2that this physiological necessity is identical with that ithose other protozoal organisms under similar circumstancewhose life-histories have been ascertained-namely, sexudevelopment.

Most zoologists hold that all animals, protozoa as well asietazoa, require from time to time to undergo sexual changes.b is true that with many of the protozoa reproduction isffected principally by a process of division or by a processf budding carried through during many generations,,undreds or thousands it may be. But there comes a time,ven in these, when the asexual reproductive energy is spent,,s it were, and when the organism concerned to avert itsextinction as a species has to assume sexual characters andeproduce sexually, a process which in some mysterious way’esuscitates its asexual reproductive faculty, thereby enablingt once more to revert to simple division or budding formother hundred or thousand or more generations. It is soM regards the malaria parasite and its congeners, and it hasbeen proved to be so as regards the humbler fresh wateramoeba. Surely the same must apply to organisms so highlydeveloped as the trypanosomes. In those blood-hauntingprotozoa whose life-history we know-again I must adducethe malaria parasites-this sexual process is carried out inthe insect vector, the mosquito, so may it be with the trypano-some in its insect vector, the tsetse fly. Indeed, special formsof the trypanosome occur in the blood of the vertebrate hostwhich, in the opinion of some observers, are early sexual formspossessing sexual characters which are found to become moreaccentuated as they are followed into the alimentary canalof the tsetse fly. These forms, which though alive, are, as hasbeen proved experimentally, incapable of multiplying in thevertebrate as the asexual forms so readily do. The reasonfor this failure of a particular phase of an organism other-wise so infective to infect is conjectured to be that thefunction of the phase concerned being sexual it lies outsidethe human body and can be carried out only in its appropriatemedium-that is to say, the tsetse fly.Such are the leading arguments in favour of a sexual

phase within its insect vector in the case of 11’ypanosomagambiense. Similar arguments apply to similar protozoa.These arguments distinctly support the law I plead for.The leading arguments against such a law, against the

occurrence of a sexual phase in the insect vectors of trypano-somes and similar protozoa, are : (1) a sexual phase has notbeen conclusively demonstrated in any trypanosome ; (2) ifthere be a sexual phase it may be passed in the vertebrateand not in the insect host ; (3) the trypanosomes can be inocu-lated artificially, sexual changes may therefore be unneces-sary for their propagation ; and (4) an insect intermediary isapparently unnecessary in at least one species of trypanosomeand therefore is not a biological necessity in Trypanosomagambiense or in any species of trypanosome.

1. A sexual phase has not been conclusively demonstratedin any trypanosome. This is one of those negative argumentsto which experience in other departments of natural historyhas shown that too much weight must not be assigned. Wemust bear in mind the difficulty in working with anorganism so minute as a trypanosome and also with one sorefractory to experimentation and dissection as a tsetse fly.Several forms under such conditions ’might readily escape

l detection. The more or less positive argument of analogy. may very well be set against this negative argument of non-; detection.

2. If the trypanosome does possess a sexual phase this mayE be passed, as in the case of certain nematodes-notably theblood worms-in the vertebrate and not in the invertebratet host. Indeed, Breinl and Kinghorn have shown that inf Trypanosoma lewisi and in Trypanosoma yccmbiense there occur- at more or less definite intervals certain cytological pheno-l mena which these observers suggest may be of a sexual- nature. If this suggestion represents the truth then theg respective insect intermediaries of these parasites may func-d tion merely as mechanical carriers. The observations re-

:- ferred to, though of great interest, have not as yet beenn carried to that point which warrants the conclusion that the’e cytological changes in question are really of a sexual nature.a Even supposing they are of this nature, it does not followv. that the sexual process is concluded in the vertebrate or that3- they are not preliminary to further and final changes in the,is insect, as in the case of the plasmodidse.ie 3. It has been argued that as the trypanosomes can bem successfully inoculated through a long series of vertebrateof hosts their propagation does not necessitate at any time aes sexual stage in the invertebrate intermediary. I do notal attach much importance to this argument. We know of

other protozoal germs which can be similarly transmitted

996

in the laboratory but which in nature are transmitted

solely by the insect intermediaries in which they have neces.sarily undergone sexual changes. The malaria and yellowfever germs have been transmitted artificially many times byblood inoculation from man to man, yet no one can denythat in nature the mosquito is the appropriate transmitter ofthese germs. Stress has been laid on the fact that in ourlaboratories the same strain of trypanosomes has been passedfrom vertebrate to vertebrate through many hundreds ofgenerations and that as yet there has been observed no signof diminishing vigour or inoculability in the parasites, suchas might be interpreted as indicating the approachingnecessity for sexual resuscitation. So far as I know, theexperiment has not been tried, but I have no doubt themalaria parasite could be similarly transmitted from man toman for many, perhaps hundreds, of generations. It is sotransmitted in the same man and that without sexual re-

invigoration. Nevertheless we know, unless it is again passedthrough a mosquito, that it dies out spontaneously in everyinstance and in a space of time something less than threeyears. Perhaps if transferred to a fresh blood it would liveeven longer than this, even without sexual reinvigoration,just as certain amoebas can be kept alive asexually beyondtheir natural term by change of culture medium. Some

trypanosome infections, including that of sleeping sickness,we know are normally longer lasting than malarial in-

fections ; it is reasonable, then, to think that they areproportionately more enduring when transmitted artificially.The argument based on inoculation experiments is, there-fore, in my opinion, of little weight.

4. The fourth argument against a general law that bloodprotozoa requiring arthropod vectors use these vectorsas a medium for sexual development is, in my opinion, themost formidable of any hitherto advanced. It is based onthe mode in which the virus of the horse disease known asdourine is conveyed. Dourine is a characteristic trypano-some disease. In nature it is contracted during coitus. Itcan readily be conveyed to other animals, but it affects

principally stallions, which convey it to, and, presumably,acquire it from, brood mares. It is conveyed and contractednaturally, therefore, in the same way as syphilis-that isto say, by contact of mucous surfaces. From this it mightbe inferred that a sexual stage in ’an insect is unnecessaryfor this particular trypanosome ; and if unnecessary forthis trypanosome unnecessary for any species of trypano-some.

Believing in the uniformity of natural operations and inthe necessity for sexual reinvigoration in all animals,including the protozoa; and believing that a sexual stageoccurs in the case of other trypanosomes, I believe it mustoccur in that of dourine-lrypano8oma eq1dperdurn,. and, aswith other trypanosomes, that it is passed in some insect asyet unrecognised.

For reasons which I shall presently explain, I conjecturethat this insect may be one which itself has acquired parasiticor semi-parasitic habits ; and, consequently, seldom passingfrom horse to horse, is not the usual transmitter of the

trypanosome from horse to horse. To compensate for thisinefficiency of its sexual medium as a transmitter, thetrypanosome by a kind of reversion to ancestral habit, hastaken on the habit of contact transmission during its asexualstage, retaining, however, the insect for sexual reinvigoration.

This suggestion will, I daresay, appear to some, probablyto most of my hearers, as being so wildly hypothetical as tobe scarcely worth considering. But when we come toexamine it a little carefully I think we shall find that,after all, it is not without support, or so highly improbableas at first sight it appears to be. Moreover, should it beestablished, it is conceivable that it might suggest an

explanation for some of the many things in epidemiologythat are still hard to understand.That so many parasites require two hosts, a definitive andan intermediary, zoologically so dissimilar as vertebrate andinsect or mollusc, has always appeared to me a remarkablephenomenon and one difficult to explain on Darwinian

principles. And yet undoubtedly it conforms to these

principles. One can readily understand how an animal,originally free, can adapt itself to parasitic life on anotheranimal, but it is very difficult at first sight to explain how itcan accustom itself to life in two absolutely different hosts-hosts so far removed from each other zoologically as a manahd a mosquito ; ’and, further, that both man and mosquito

1 are essential for its welfare; and, moreover, that in one. host-in this case the vertebrate-the parasite has an

r asexual life and in the other host-the insect-a sexualr life. How by any recognised principle of evolution can a7 life so complicated be attained or explained ?z I would with great diffidence and without entering ondetail submit the following hypothesis. Vertebrates, arthro-l pods, molluscs, helminths, protozoa have all of them

sprung from a common ancestor, or, if not from one commonL ancestor, from similar ancestors. Very early in the growthI of the family tree a certain originally free organism became: at first intermittingly, then finally and permanently, parasitic: on another organism. In time a definite host and parasite, relationship was established between the two. From the, original host varieties, species, genera, and so on were

gradually evolved. Concurrently with this evolution in thehost the parasite, just as its host had done, adapting itselfto -its changing environment, evolved new varieties, species,genera, &c.

In the course of these concurring evolutionary processes,’there came a time when, say, the insect and vertebrate strainsbegan to diverge. A certain organism was parasitic on thecommon insect-vertebrate ancestor. The process of evolu-tion in this host-ancestor being necessarily very gradual, theparasite-as is the case with many existing parasites-was.capable of adapting itself to the closely related varieties ofthe host, among others to the insect-resulting strain and to.the vertebrate-resulting strain. Divergence in these host-strains continuing, varieties became species, species genera,and so on, until insect and vertebrate, as they exist at thepresent day, were evolved. "

In the early stages of the evolutionary process the parasitecould live in either vertebrate strain or inseet strain of host

indifferently, but there came a time when it was often moreto the advantage of the parasite to pass its sexual life in theancestral insect strain, its asexual life in the ancestral’vertebrate strain. In the process of evolution this at firstmore or less accidental habit-I can hardly apply the expres--sion "optional habit" to a parasite-became fixed and hasbeen transmitted, so that now the sexual life of the malariaparasite is passed in the mosquito, its asexual life in man.

I This is my explanation of the double life, if I may so"

describe it, of so many and so widely separated parasites,including protozoa, nematodes, trematodes, and cestodes. Ican explain it in no other way ; the explanation I offer seems..to harmonise the facts and to conform to the doctrines ofevolution.

In the case of every double-host-using parasite it is ob-.vious that both hosts must be organisms that are in frequentand fairly close association, otherwise the parasite employingthem would lack the opportunity of passing from one to theother. Thus it comes about that the parasites of theherbivora are at another stage of their existence parasites of-the carnivora ; the hydatid of the sheep, the tapeworm of thedog ; the trematode of the sheep, the cercaria of the swamp-haunting mollusc ; the blood worms of man, the larval’nematode of the mosquito. This is obvious; opportunities of’passage from host to intermediary, and from intermediary tohost, must be of sufficient frequency, otherwise the parasite-demanding them would necessarily cease to exist. -

At first sight one would think that the more intimate and’frequent the association of definitive and intermediary host.the better the opportunity for the parasite. Thus one wouldthink that a louse, or an itch insect, or a Demodex folliou.-lor1lrn, being permanently in residence on its vertebrateassociate, would be a more suitable intermediary for amalaria parasite than the mosquito is. But we know that itis not so, and one of the reasons for this undoubtedly is thatthese ectozoa comparatively rarely pass from vertebrate to-

vertebrate ; whereas the mosquito is in the habit of bitingone man one day, and it may be quite another man a fewdays later, and so constitutes a most efficient go-between and!vector of blood parasites.But now another principle comes into operation in this

complex of parasitism. Insect and vertebrate life havebeen evolved side by side, springing from a common’ancestor. I have endeavoured to explain in what way theparasites they possess in common have been evolved con"currently and along with them, and I have attempted anexplanation of the phenomenon of definitive and inter-

mediary host, and to show that this is no fortuitous relation-ship but a necessary one, and one in entire harmony with the

997

doctrines of evolution. I have endeavoured to explain how a fcertain intimacy of association between intermediary and sdefinitive host is essential for the parasites employing them, Iand how this association must not be confined exclusively, as 1regards either host or intermediary, to a single individual of <

-each or either.The protozoa and possibly the nematodes acknowledge, in

my opinion, a very remote ancestry-that is to say, theybecame parasitic very early in the growth of the phylogenetictree. There are other parasites, however, which manifestlymust have adopted the parasitic habit very much later in the’history of the animal kingdom. Certain insects, whichprobably from the beginning were closely associated withwertebrates and lived on the juices of these vertebrates,finding that they no longer required their wings, gra-dually dropped these wings and permanently attachedthemselves to their vertebrate food source. Such are

many of the hemipterous and apterous insects, lice, &c.

,Similarly the ancestors of the acari, of some of the ticks, andother ectozoa have gradually fallen into complete or partialparasitic habits ; certain bugs and ticks are even at the

present day in process of acquiring this habit. I have nodoubt that, as with the modern mosquitoes, ticks, and bugs,the ancestors of the existing huge ectozoal fauna of manand other vertebrates fostered parasites which they possessedin common with their respective vertebrate associates.What, you may ask, has become of these parasites ?Have they failed to do what other parasites and-the hosts of other parasites have succeeded in doing ;have they failed to adapt themselves to their graduallychanging environment ? And if they have succeeded in

.adapting themselves how did they manage to overcome

certain obvious difficulties, for example, that which I haveindicated as being so necessary to such parasites, the

go-between habit of at least one of the hosts, that

necessity which is so efficiently subserved in the case ofthe malaria parasite by the mosquito ?

I believe that this has been effected by a processof reversion, the asexual form of the parasite graduallyre-acquiring, for purposes of propagation, the capacity andhabit of direct passage from vertebrate to vertebrate,the necessity for sexual reinvigoration from time to time

being still subserved by the ectozoal descendant of an

originally free insect or other arthropod.That is how I would explain the apparent absence of an

insect intermediary in the trypanosome disease, dourine.Some apterous, hemipterous, or semi-parasitic insect phylo-genetically allied to the tsetse flies is its intermediary. Thisinsect has not been found, probably because it has not beenlooked for in the proper way.

I hold, therefore, that the existence of a sexual phase inthe sleeping sickness trypanosome, Trypanosoma gambieitse,and other trypanosomes is more than probable, that it has no1been disproved, and that the argument founded on th<natural direct communicability of dourine in the apparen-absence of an insect intermediary for its germ, Trypanosomeequiperdum, is not valid, and that the evidence hithertcadduced is distinctly in favour of a law to the effect that bloodhaunting protozoa having arthropod vectors require, and makuse of, these vectors for necessary sexual development. Wh;the sexual stage of these parasites is passed in the arthropol- and not in the vertebrate I cannot explain, any more thanean explain the contrary arrangement which obtains in thblood-haunting nematodes, the sexual stage in their casbeing passed in the vertebrate host, the asexual in the insect

I have no doubt, while listening to these remarks, it haoccurred to some of you, as it has often occurred to mEthat the principles I have endeavoured to express havewider application than that which I have directly indicatecthat our disease germs and our ectozoa-insignificant thougthe latter appear to be-are correlated more frequently thais generally suspected, that, in fact, there is a necessar

relationship between them. Indeed, in some instances w.are beginning to find this to be the case. I have no doulsome of you dimly perceive that the whole of this subjecwhich recent studies in tropical medicine have done so mucto develop, may have important practical bearings, that itnot an exclusively tropical one, and that in the near futu’it may find an application in the explanation of the pathgenesis and, therefore, an application in the preventionmany diseases of temperate as well as of tropical climateIt is a tempting theme to enlarge on. I must forbear.

;el I have already been sufficiently hypothetical. Perhaps)me future Huxley lecturer will atone for my sins in thisaspect and supply the facts which, I acknowledge, are stillLcking fully to establish the several hypotheses I havendeavoured to express.

THE TREATMENT OF INOPERABLECANCER.1

BY HENRY MORRIS, M.A., M.B. LOND.,PRESIDENT OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND;

CONSULTING SURGEON TO, AND EMERITUS LECTURER ON SURGERYAT, THE MIDDLESEX HOSPITAL, LONDON.

WHEN the Central Committee of the International SocietySurgery honoured me in March, 1906, by asking me to readpaper at the Congress in 1908 on the treatment of inoper-le cancer they were, I believe, aware that I had opened ascussion on the same subject at the meeting of the Britishedical Association at Manchester in August, 1902. It is

)w, as I write, about five and a half years since that dis-tssion took place, and with but little exception the questionands to-day much as it did then. Increased experienceid the mere lapse of time have enabled some of the methodsLen under consideration to be more justly appraised, andrtain others which have since then been claimed to betllcer cures have been brought forward, but there has been,nfortunately, no definite advance towards the discovery ofreliable cure. If, therefore, I borrow somewhat freely

’om my former paper, it is on the old Greek principle thataving once said what one wished to say, one can hardlyay it twice, &dgr;is &dgr;&isin; ovrc except by repeating one’swn words.I will begin by quoting verbatim the definition I gave in

902 of the meaning of the terms the treatment of inoper-ble cancer."

"The term cancer’ is used in a general sense to include,11 forms of malignant new growths, and therefore embracesodent ulcer, sarcoma, and lympho-sarcoma, and endo-helioma as well as epithelioma and other varieties of carci-ioma. The term ’ inoperable’ means that the disease;annot be entirely eradicated, or permanent immunity hoped’or, by a cutting operation, or by the actual cautery, or anyscharotic aiding the knife. It does not imply that malig-aant disease is of constitutional as distinct from local originand that as such it is ineradicable. On the contrary, I takeLt for granted that cancer is at first, and so far as rodentcancer is concerned throughout, a local disease. But even onthis view there are four groups of inoperable cases. Theyare : (1) primary cancer affecting inaccessible parts andorgans ; (2) primary cancer which though originating in anaccessible part or organ of the body has been allowed toextend beyond the limits within which an operation is

prudent and complete removal possible ; (3) certain cases ofacute diffuse carcinoma and very rapidly growing or widelyinfiltrating new growths of exceptionally virulent character ;and (4) recurrent cancer, where the disease has recurred inmultiple metastatic foci or in parts beyond the limitsof removal. Many of the cases included in these groupsare submitted to operation for the purpose of palliatingsymptoms or prolonging life. Hence the term treat-ment’ as applied to inoperable cancer means one

of two things: (1) the employment of remedies andmethods other than the knife, to cure, ameliorate, or retardthe disease, as well as to prevent relapses after its removal ;or (2) the employment of the knife to give relief from pain,to prolong life, to restore function, and otherwise to makethe patient’s condition more tolerable."

PALLIATIVE OPERATIONS.In a paper which is intended merely to introduce a dis-

cussion it is of course quite impossible to consider all the

many palliative operations which are resorted to in cancer

of the various organs and regions of the body. Only theprincipal methods employed to combat cancer in the organsand parts most commonly affected will be referred to andthose only with regard to their reputed or -accreditedbeneficial results.

1 A paper read at the International Surgical Congress at Brussels onSept. 24th, 1908.