The Causation and Spread of Epidemic Influenza

Prior to 1933, aetiological studies of human influenza yielded little precise information. In 1938 Shope showed that swine influenza, the analogous disease of pigs, was caused by a bacterium (Haemophilus influenzae suis) and a virus, in symbiosis. Two years later, Smith et al reproduced the signs of influenza in ferrets by the intra nasal injection of bacteria free garglings from cases of human epidemic influenza. The suspected virus aetiology was thus confirmed. This classic WS strain of the virus, and all subsequently isolated, serologically related strains were collectively designated the “influenza A” group of viruses. At least two other major serological groups have since been identified and these have been designated “B” and “C” respectively. Epidemiological studies have indicated that epidemic influenza, in its widespread form, is caused by viruses of the A group.


T h e P r in c ip le s a n d P r a c t ic e o f M e d ic in e
A C o m p a n io n in S u r g ic a l S tu d ie s Second Edition. By IA N A IR D , Ch.M., F.R.C.S., F.A.C.S. 1314 pages 84s.

T h e C o m p a r a tiv e A n a t o m y a n d P h y s io lo g y o f th e N o s e a n d P a r a n a s a l S in u ses
By SIR F.R.C.S. 418 pages VICTOR NEGUS, M.S.. Editorial It seems to the student of medicine that arguments about the method by which his education can be accomplished with most effect, will never cease. Thus he is perpetually hearing, from this source or from that, that one system is better and another worse, one more and another less suited to turn a doctor loose upon an unsuspecting and at times positively unfortunate public. The system of teaching students in small tutorial groups has many advantages, and the existence or an intimate student-teacher relationship will always rank high amongst them. This system of education which is practised in a number of English universities is in marked contrast to the Scottish university system which consists of a formal lecture course, accom panied by clinical instruction in scarcely less formal cliniques. The lecture course tends to be authoritative and up to date since it is usually shared out amongst a number of lecturers, each dealing with that aspect of the whole subject in which he is specially interested. Further, in contrast to the Tutorial system the course can be carefully planned in advance, and each aspect treated in due perspective since the student cannot divert his teacher's attention from the main stream of thought. None the less it must be admitted that there are many students who find the process of expressing their own views before an intelligent audience, or equally of criticising the expressed views of their fellows, an instructive and a stimulating exercise. It is of course true that when in clinique, the student is often allowed, sometimes even encouraged, to discuss his teacher's views in a critical fashion, but, unfortunately, time is limited and the cliniques manifestly overcrowded. Here is a deficiency in our education for which the Royal Medical Society attempts to compensate, and it is our claim that we provide facilities for the student to become a more able speaker and a more critical thinker. A sense of duty need not be the excuse for a student to join the Society, because an evening at the Royal Medical is spent in good and friendly com pany and needs no further recommendation than its own excellence. It combines the teaching potential of a group study session with the pleasure of good fellowship and entertainment.

C o m p le te C a ta lo g u e sen t on re q u e s t T E V I O T P L A C E , E D I N B U R G H
Gilbert Blane, a President of the Royal Medical Society in 1784, said of the Society's founders, on the occasion of the purchase of the new h all: "Here they learned to reason and think for themselves; here they combated prejudice and error, however sanctified by antiquity and authority, and it was here that they learned to love and esteem each other and to cement the bonds of true friendship, a friendship severe and durable inasmuch as it was founded on a virtuous and liberal intercourse." lies Medica has now entered its second year, and although its achieve ments so far are not to be depreciated, it is now encountering new problems along the road to establishment and maturity. The members of the first Editorial Committee shouldered their responsibilities with a pioneering zeal and Res Medica will indeed be fortunate if its future committees are of the same calibre.

RES M EDICA
The aim now must be to establish a tradition for the Journal which will be as durable and as honourable as that of the parent Society. Advance in this direction depends on the members keeping in mind that the sole purpose of the Journal is to be of service to the interests of the Society. Res Medica will become more and more effective in doing this if, after the novelty has worn off, the members continue to show an interest in its progress. Of all the invitations one has ever been privileged to receive, I wish you to know th at the arrival of your own was a special honour, and a special delight to accept-giving m e, am ong other things, the opportunity to re-visit the house of our ancient Society, and to recall a t close hand m any happy occasions within these walls some thirty years ago. It was the tim e of the great Sir A lfred Ew ing as Vice-Chancellor, and, in the M edical School, of Sir John F raser and Sir D avid W ilkie of glorious m em ory, whose portraits adorn your walls. We generated then, as doubtless you generate now, abiding affection for E dinburgh and its University, and not only affection but I confess it, sentim ent, for our R oyal M edical Society. R eading the leading article in the second num ber of Res Medica, I have been greatly struck by its closing sentences: "A t a tim e when religions, cultures and individuals are m enaced by nuclear weapons and foreign ideologies, living traditions assum e an im portance never envisaged by their inaugurators. L et us then foster unity and friendship and be worthy heirs of our heritage." This is the ever-renewing and ever m ore significant function of the Royal M edical Society, and I esteem the great honour of inaugurating your two hundred and twenty-second Session. I m ention these things to show how it is and why, th at I received your invitation with such pleasure and gratitude.

1958
I have taken as my subject the history and the prospects of cancer research. I t could be regarded as a m orbid one, but I hope to show that this is not necessarily so; on the contrary, th at the history of the field is rom antic and inspiring, th a t its present state is active and exciting, and that its future-although by far the greater part rem ains to do-is full of hope and promise.
C ancer research can be regarded from two aspects-the purely m edical, as a great endeavour directed to the solution of a hum an problem ; and scientifically, from the unique character of the disease, as an integral part of m odern biology. It is unique since its basis lies in a perm anent accession in the growth of cells. Its history has largely been coterm inous with that of the m icroscope, perm itting the developm ent of the cell theory, which has been described as one of the greatest conceptions of the hum an m ind, and which, although it had m any precursors, was finally established as recently as the early p art of the nineteenth century.
It is often said th at the cancer cell has acquired the power of unlim ited growth. This is strictly not so, since m ost norm al cells are equally capable of unlim ited grow th in appropriate conditions. M ore and m ore certainly, cancer appears rather as due to the release or unm asking of that growth potential which cells all along possess, although exquisitely restrained. T he mechanics of cell division appear devised to effect an equal distribution. Yet soon in developm ent is superposed the mysterious feature of differentia tion, while the rate of growth declines. Even in the adult, however, cell division continues, either tem porarily as in the healing of wounds, or con tinuously as in the tissues of the bone m arrow , intestine and skin. T he m ain feature here is a matchless orderliness and precision. In the words of D r Isaac W atts in one of his hym ns, " Strange th at a harp of a thousand strings, should keep in tune so long." Sooner or later, however, a single cell may becom e transform ed to a cancer cell, with altered grow th properties which are now and henceforth no longer subservient to the needs of the body, but independent and frequently autonom ous. T he liability to this change appears inherent in all cells capable of growth. It is not surprising, therefore, that we should find evidence of it throughout the whole of the plant and anim al kingdom , not only in historic b ut also in pre-historic times.
So far we have spoken of the nature of cancer. W hat of its cause or causes? M odern cancer research largely dates from the tim e of R udolf Virchow, whose Die Cellular pathologie was published alm ost exactly one hundred years ago. R em em bered for his dictum omnis cellu la e cellula, he applied the cell theory to pathology, and inaugurated several decades of investigation of the m icroscopical structure of cancer in m an and anim als, carried out first in the great schools of Germ any and then the world over. A lthough historically necessary and im portant, this was not, however, sufficient. T ow ards the close of the century a need becam e ever clearer, namely, for the use of the experim ental m ethod. In this country, the new outlook led in 1902 to the establishm ent of the Im perial C ancer R esearch Fund, and in 1909 to th at of the R esearch Institute of the C ancer H ospital in London. The first director of the form er institution was E. F . Bashford, who with great genius and foresight, and with the support of a small but brilliant staff, was able within a brief ten years to lay the m ain foundations o f the whole subject, and to forecast its likely developm ent and requirem ents for many further years ahead. All this helped to prom pt, or was accom panied by, sim ilar developm ents in the U nited States, in E urope, and in Japan.
A lthough purely m edical m ethods alone were to prove insufficient, it should be noted that the first and vital clues arose from observations m ade in the; field of occupational and industrial m edicine. T ow ards the end of the eighteenth century, Sir Percivall Pott had described the special liability of chim ney sweeps to cancer of the scrotum , and had traced the cause to contam ination of the skin with soot. W ith the industrial revolution cam e m any m ore exam ples, m ainly due to occupational exposure to m ineral oil and tar. A notable case was the so-called " paraffin cancer" in the Scottish shalefield, described by the celebrated Joseph Bell, of whose association with the R oyal M edical Society we are justly proud. E xperim ental proof th at m ineral oil, coal tar and pitch do in fact induce skin cancer had, however, to be long deferred, indeed until 1915, when Y am agiw a first pro duced cancer artificially through chemical m eans, by applying coal tar to the skin of the rab b it ear. Coal tar being a complex m ixture of a great host of chem ical individuals, the search then began for the responsible agent o r carcinogen. In the early 'twenties, Bloch in Z urich adduced evidence th at the agent m ight be a com plex hydrocarbon, th at is, a com pound con taining hydrogen and carbon only-and virtual proof of this was later obtained by my own predecessor, Sir E rnest K ennaw ay, at the C ancer H ospital. T hrough his w ork and th at of his school, the picture gradually em erged of carcinogenic substances b u ilt through the conjugation of benzene rings.
E arly in these investigations, it was repeatedly noted that cancer-producing tars exhibited the property of fluorescence in ultraviolet light, th at is, to absorb invisible light of short wave-length, and to em it visible light of longer w ave-length. In 1927, W. V. M ayneord, again at the C ancer H ospital, took C A N C E R R E S E A R C H : ITS H IS T O R Y A N D PR O SPE C T S 9 the m atter decisively forw ard when he indicated that the fluorescence spectra of such tars showed qualities which appeared to be characteristic. This spectrum of cancer-producing tar proved to be, in K ennaw ay's words, "the single thread tha t led all through this labyrinth," and it soon enabled him, and his colleagues, to track down the carcinogenic agent. Since it was already suspected to be a com plex hydrocarbon, the next step was to exam ine the spectra of those polycyclic hydrocarbons already know n in pure form , and constituted from the fusion of various num bers of benzene rings. Very shortly, H ieger was able to m ake the key discovery th at 1 :2-benzanthrace (com prising four such rings), also possessed the characteristic spectrum . By a curious accident, C lar in 1929 had just described the synthesis of the related hydrocarbon containing five fused rings, {1 :2:5 :6-dibenzanthrucene), and in the sam e year K ennaw ay and H ieger proved this substance to be carcinogenic in mice-the first pure chem ical individual to be recog nised as possessing this property. T he fluorescent spectrum was also used to great purpose in the isolation of the naturally-occurring carcinogenic agent from pitch. This proved to be another pentacyclic arom atic hydrocarbon, namely 3 : 4-benzpyrene, which C ook and Hew ett were soon (in 1933) to prove by synthesis. In the sam e year, Cook and H aslew ood produced methylcholanthrene from a bile-acid, so raising the whole question-still undecided-w hether traces of highly potent carcinogens can be form ed in vivo from perturbations of the norm al m etabolism of steroids. A chief result of all this work was eventually to provide an amazingly satisfying and com plete picture of the relationship existing, within this series, between chemical constitution and biological action.
In the intervening years, m any older chem ical classes had been uncovered, in no way related to the cyclic hydrocarbons, b u t equally endow ed with carcinogenic qualities-various arom atic am ines, especially those involved in the causation of cancer of the bladder; a host of azo dyestuffs with the special propensity to evoke tum ours of the liver; a series of aminostilbenes with very diversified carcinogenic properties; and m any others. T o these we m ust add a great range of purely physical agents, including ultraviolet radiation itself, X -rays, radium and thorium , and a host of radio-isotopes arising from the atom ic energy program m e, especially radiophosphorous, radioiodine and radiostrontium . Of late we have also recognised the carginogenicity of m any m acrom olecules and plastics, and the special function in carcinogenesis which may be played by the m etals, as also the role of m any biological agents, e.g. those viruses responsible for the induction and propagation of certain tum ours in anim als (although not so far in m an)topics any one of which could easily exhaust a whole lecture in itself.
In none of these cases have we precise know ledge of the m ode of action, or of the site a t which it is excited within the cell. Only in the past few years have there come certain hints, through the discovery of carcinogenicity in yet another chem ical class, nam ely the nitrogen m ustards-substances developed in the Second W ar for the purpose of chem ical w arfare, and nitrogen analogues of that sulphur m ustard or " m ustard gas" which had been used in the W ar of 1914-18. T he nitrogen m ustards have the advantage of relative chem ical sim plicity, with features which are suggestive, or even indicative, of possible modes of action. T he action upon dividing cells is highly direct, leading to cytological abnorm alities indistinguishable from many which can equally be produced by ionising radiation. On this account they are not unreasonably described as radiom im etic, and it is certainly rem arkable th at just as X -radiation is em ployed in the treatm ent of cancer, so also can some of the m ustards, in the palliation of certain form s a t least. Contrariw ise, just as X -rays can be cancer-producing, so also can the m u stard s. In m any cases th e tu m o u rs so p ro d u c e d b e a r signs-as a kind o f im p rin t-th a t th e actio n has involved th e nuclei a n d ch ro m o so m es. A ce rtain e x ten t o f chem ical reactivity is re q u ire d , suggesting a g a in th a t the b io lo g ical e n d -resu lt m ay d ep en d upon re actio n w ith so m e ce llu lar c o m p o n e n t so fa r undefined. T h e m ain featu res of the nitro g en m u stard s is th eir possession of tw o o r m ore h alo alk y l side-chains. W ithin th e series this indeed ap p e a rs to be a re q u ire m e n t fo r biological activ ity , a n d led to the p ro p o sa l th a t activ ity m ig h t in fa ct d ep en d upon ch em ical cross-linkage, as fo r ex am p le betw een th e co n tig u o u s lin ear m acro m o lecu les of the ch ro m o so m es th e m selves. A lth o u g h this hypothesis is now kn o w n to be u n d u ly sim ple, it proved trem en d o u sly fru itfu l in dev elo p m en t, lead in g for ex am p le to th e ap p lica tio n of m u ch k n o w led g e a lre ad y a v a ila b le in the field of cross-linking agents in tex tile technology, a n d hence to th e ra p id discovery o f o th e r series w ith s im ilar bio lo gical effects-epoxides, p o lyethylene im ines a n d dim esyl c o m p o u n d s-now classed u n d er th e g en e ral h ea d in g of b io lo g ical alk y latin g agents.
T h e ex a ct n a tu re of the b io lo g ical re cep to r is still no t k now n. It is very p ro b a b ly genetical in fu n c tio n , as re actio n w ithin the nucleus a n d upon the ch ro m o so m es m ight infer. H o w ev er, su ch re actio n w ould certain ly in tro d u ce w id esp read rep ercu ssio n s in the cy to p lasm , a n d d irec t action by certain carcin o g en s u p o n the o rganelles of the cy to p lasm is by no m eans excluded. N o tw ith stan d in g , a p ro m in e n t c a n d id a te fo r the seat of action of th e ca rc in o genic a lk y latin g agents is w ith o u t d o u b t-a n d fo r m any reasons alth o u g h n o n e is as y e t decisive-th e d eo x y rib o n u c leic acid of the ch ro m o so m e stru c tu re, as th e chem ical basis o f cell genetics a n d heredity. A g re at im p etu s has b een given to these studies by the p ro p o sa ls fo r nucleic acid stru c tu re pu t fo rw a rd by C rick and W atso n -of the b o n d in g of p y rim id in e a n d pu rin e b ase p airs to yield essentially su p erp o sa b le stru ctu re s, a n d o f the co m p le m en tary d isp o sitio n of these as bridges in a d o u b le helix of p h o sp h ate-su g a r chains; a n d we alread y h av e som e precise chem ical in fo rm atio n as to the ac tio n u p o n such a stru c tu re b o th of ionising ra d ia tio n s an d of the ions y ield ed by a lk y latin g agents. B ut fu rth e r ad v a n ce m u st largely d ep en d upon o u r d ee p er k n ow ledge of ch ro m o so m e stru c tu re . W hile w aiting, we can gain m uch th ro u g h the use of w h a t is still th e m o st fa v o u ra b le m a te ria l-nam ely th e g ian t ch ro m o so m es of th e salivary glan d of th e fru it fly Drosophilain stu d ies of th e chem ical basis of biological m u ta tio n generally, of w hich carcin o g en esis m ay be a special case.
A ctin g upon such m ateria l, the a lk y latin g ag ents freq u en tly p ro d u c e changes of the n a tu re o f d eletio n , and this, w ith o th e r co n sid eratio n s, has led to th e view th a t ca n cer ca u satio n could b e d u e to c o m b in a tio n of the ag en t w ith nucleic acid, so lead in g to defects in its synthesis o r stru c tu re . T h is process w ould in te rru p t the essential p re cision of th e nucleic acid , a n d p rev en t th e fo rm a tio n of certain protein m olecules (a n d especially p erh ap s g ro w th -reg u lato ry enzy m e-p ro tein s vital to th e c o n tro l of n o rm al cell d iv isio n ), fo r w hich we kn o w the integrity of th e nu cleic acid stru c tu re is necessary a n d responsible. In th e case of the carcin o g en ic h y d ro c a rb o n s a n d azo-dyestuffs, th ere is also evidence th a t the sam e deletio n of key p ro tein s can be b ro u g h t a b o u t by co m b in atio n of the carcin o g en w ith p rotein m olecules them selves, directly.
W e th e re fo re a p p ro a c h the view th a t carcinogenesis is a process of b io lo g ical m u ta tio n by loss, an d th a t th ere is no tru e acq u isitio n of a new g ro w th p ro p e rty on th e p a r t of th e can cer cell, b u t ra th e r th e u n m ask in g of th e g ro w th p o ten tial w hich its n o rm a l p re cu rso r h ad all alo n g possessed. T h e g en eral co n cep tio n h as still to b e tested , a n d could clearly h av e th e w id est im p licatio n s. T h e re is an increasing n u m b e r of diseases recognised as d u e to enzym e deficiency, a n d som e o f them can b e co n tro lled by re sto r ing th e defect th ro u g h a k in d of su b stitu tiv e ch e m o th e rap y . It w ell m ay be.
in the future, th at cancer too will fall in this class, and becom e am enable to control through a re-im position, from w ithout, of that grow th regulation which the cancer cell itself has lost forever. A t any rate it can fairly be said we are at least approaching certain correlations, between the reactive properties of given carcinogens, the places a t which and the m ethods by which they com bine in the cell, and the perm anent alterations in growth behaviour, which com e about as the result. A lthough so m uch rem ains to do, the story is great and growing. W hen one day it comes finally to be told, it will be seen to have m eaning far beyond the sphere of m edicine alone, and to be in p art a m odel of w hat can be achieved by the hum an m ind through the interaction of biology, chem istry and physics.
I end as I began, with thanks to the Society and all its m em bers for this kindly privilege, I also wish to record special indebtedness to my colleague M r K. G. M orem an, and to the officers of the Society for indispensable assistance. M ay the Society enjoy strength and prosperity not only in the present new Session, but in all those which lie ahead, in a future which we are confident will continue that unfolding of the art, science, and achieve m ents of M edicine, tow ards which the Society itself, in its long history, has m ade no m ean contribution.

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THE SOCIETY'S LIBRARY
Based on a Dissertation read before the Royal Medical Society on Friday, 28th February 1958.
By J. J. C. CORMACK Amongst all the inventions, attainments and discoveries which have marked M an's strange progression from Darwinian prehistory to this modern, hectic but stimulating civilisation, the realisation of his ability to communicate his thoughts and ideas in permanent form must rank extremely high. Few will deny that the discovery of writing, the manufacture of paper and the invention of the printing press are among the greatest landmarks in human history. Certainly in Medicine we can consider books to be amongst the most useful and basic of the tools of our trade-for here we can draw upon the wisdom and learning of preceding ages and it is here that we have contact with the minds of those generations of our predecessors who have risen and passed away. We in this Society rightly value the traditions of our past and I make no apology in presenting briefly some facts and some thoughts on that greatest of our links with the past-and not only with the past but with the future as well-our Library. I should like to tell you something of its history and of its present state; I should like to whet your appetite for exploration by exhibiting a few of its treasures and I should like to evaluate the place of the Library in the Society's life, and its prospects for the future. It is not surprising that a Society such as ours should have wished to acquire a representative collection of medical books. That it began to form its Library early is shown by the fact that sixteen years after the Society's formal foundation, in 1753, a library was being accumulated in the room set aside for the use of the Society in the old Royal Infirmary; books being purchased with funds which had previously paid for tavern accommodation. This room soon became inadequate; the Library being " not in such a situation as could be desired either with regard to conveniency or preserva tion." In 1755 the foundation stone of the new Hall was laid by the venerable Dr Cullen. This Hall, which is well known to us from Shepherd's engraving, stood in the south west corner of Surgeons Square-the site of which is now the courtyard of the Physics Department in Drummond Street. In 1778 the Society petitioned the King for a Royal Charter, and among their reasons for so doing they instanced "That the Society, by contributions of the Members have gradually made a collection of Medical Books, which is daily increasing ..." This Charter was granted on 14th December 1778 and now stands in the Society's Hall.
In November 1852 the Society moved to its present premises. The old Medical Hall stood on ground which was needed for extension by the Managers of the Royal Infirmary, and after prolonged negotiations the Society sold the old Hall to the Infirmary for £1700 and moved to 7 Melbourne Place, which it was hoped would provide "full accommodation for the Library, now amounting to 14,000 volumes, selected with a care unexampled in any other institution." Throughout the ensuing years the problems of sorting, listing and cataloguing the Society's books presented constant worries to each successive Library Committee. Our earliest extant copy of a catalogue is one published in 1812, and the one which is most up to date, and by which this Library is known elsewhere, was published in 1895. Continually efforts were being made to carry on with cataloguing and indexing the Society's volumes, but the struggle was an uphill one and repeated agonised appeals to members for help in this work seemed to be of little avail.
A great step forward was taken in 1937 when the room opposite the Bramwell Room was renovated and set aside for our oldest and most valued books (including the Dissertations) as a memorial to J. R. Young. A further most shrewd and progressive step was taken in 1956, under the Librarianship of J. G. Birkbeck, when some 1000 works of non-medical interest, having been vetted beforehand, were alienated and sold for a gratifyingly large sum of which a proportion was invested for the use of the Library Com mittee and the remainder used for some much-needed redecorating.
The present time sees the start of a new venture; with the generous financial assistance of the Carnegie Trust we have been able to obtain expert help in the much-needed work of re-cataloguing the Library. The devoted skill of Miss Wingate has already accomplished a large part of this mammoth task. With this work in hand, and with the newly established appointment of an H onorary Librarian to act as "guide, philosopher and: friend" to successive Librarians, thus ensuring a measure of continuity, the Library would seem to be taking on a new lease of life.
W hat does this, our present Library, comprise? Approximately speaking some 11,700 volumes, falling roughly into the following seven categories: 1. Space does not permit me even to review the cream of this collectionit must suffice for me to say that the whole sweep of medical history, and more, the history of our own Society, is mirrored here-from the early fathers H ippocrates, Aristotle, Galen, Celsus and Avicenna, through Vesalius, Eustachius, Harvey, Willis, Cullen and Boerhaave, the Monros and the Hunters, Simpson, Syme and Lister, down to the most modern authors. To illustrate but two of our treasures we have here a page from the works of Ambroise Pare-a truly fascinating volume from the pen of the father of modern surgery and a giant among men; and this rare link with the discovery of digitalis-Withering's "Account of the Foxglove" with its inscription to the Society.
We should be proud to possess these volumes, but at the same time we must be aware of the problems which face us in our responsibility for caring for these treasures and also ensuring that the Library gives the best possible service to members.
It will probably be clear from what I have already said that the major interest of this Society's Library is a historical one. For many years now it has been the case that the Society has been unable to keep a stock of current textbooks which can be lent out to members. This type of service is provided by our subscription to Messrs Ferriers Lending Library, and with the increasing speed with which new textbooks or new editions of old textbooks are being published, I do not think that the Society will ever again be in a position to organise any large-scale lending library facilities of its own. It may well be that if the Society increases its membership we should augment our already overburdened subscription to Ferriers. 14 RES M ED IC A This lending service is supplemented by the current textbooks available in the Consultation Press, it is imperative that this section of our Library should be kept as up to date as possible, and indeed that it should be enlarged as soon as financial circumstances permit. Ideally it should contain an entire collection of the standard textbooks and books of reference currently in use at this School. This ideal has not been fulfilled, but it should certainly be our aim. We should also aim to have the older books which we possess in proper order, and in such a state that members will be able to find any particular volume with ease. Members should also be able to browse through some of the books which have been written and read by their predecessors without running the risk of covering themselves with the dust of ages or having precious tomes disintegrate in their hands.
Obviously the major work of re-cataloguing is the first step towards restoring the Library to its rightful usefulness. Work has already started. How is it to proceed? First of all the volumes in each room must be classified, as far as the limitations of the shelving will allow, into subjects-this is the work which is proceeding just now in the North Library-then the major task of completing the card-index author catalogue and the subject-index will begin.
When this preliminary work is completed the Library Committee and the Society will be faced with important decisions concerning the alienation of books. We have quite a number of duplicate volumes on the Library's shelves which should almost certainly be sold. There are also in many cases numerous editions of popular textbooks-in these instances it might be best to keep copies of the earliest and latest editions and discard the remainder. On these issues it may be relatively easy to decide, but more difficult problems of alienation present themselves. Many of our books are written in a language no longer understood by the majority of medical students-namely Latin. We have also some works in Greek and a considerable number in French and German. How many of these are worth keeping? Obviously it will be for the Society to decide at a later date; personally I feel that many of the medical classics of the 16th and 17th centuries should be most carefully preserved and cherished, and if possible that they should be supplemented by English translations where such are available. Even if their content is not fully understood they illustrate the steps which have been taken from earliest times along the road of medical progress.
However, it is more doubtful whether many of our 18th and 19th century German and French works are really of much value to the Society either for instruction or for interest. Some, though not all of them, may well be taking up space on the shelves when they could serve better purpose by being sold and providing money for much-needed improvements. We also possess odd incomplete sets of Journals of doubtful value and their alienation too will require to be considered. But I must emphasise that it would be the utmost folly to consider such pruning of our collection before all the books are listed and indexed, and when the time comes we shall certainly need to obtain the most expert advice. Too often in the past zeal and enthusiasm have outrun discretion, and sound schemes have been defeated by precipitate action.
After we have decided what we wish to discard and what to retain, in the light of the value of the main bulk of the Library to the Society as an historical collection which mirrors both the history of medicine and the history of the Society, the next step will be to decide on the proper lay-out of the Library.
Once a decision is made on this, books will have to be shifted to conform. This may mean large scale upheavals, but it will be worth doing if the job is to be properly completed. This finished, permanent shelf marks T itle page of W ithering's Account of the Foxglove which he donated to the R oyal M edical Society.
Page from the C ollected W orks of A m broise Pare showing restitution of dislocated shoulder.
can be allocated to books and the catalogue then completed. As far as possible the books in the North Library and Museum would be in logical categories, but the provision of shelf marks would certainly mean that by using the catalogue any particular book could be rapidly traced. A t this juncture the Society should be in possession of a complete card-index author catalogue and subject index of all its books. A decision will then have to be made on the publication of a revised catalogue to replace the 1896 edition. Owing to high costs of printing it might be advisable to restrain our ambition in this direction, but even a cyclestyled copy of an up-to-date author catalogue would be of value for the information of other libraries and interested bodies and for our own prestige, as well as its obvious use to members. Once we have a catalogue it will be imperative that successive Librarians keep it up to date. As our rate of expansion is now not high (nor is it desirable that it should be) this task will probably not be very onerous, but it will be most important. With the appointment of an Honorary Librarian the problem of continuity should be at least partially solved.
However, even with our Library pruned, re-sorted and re-catalogued, we will still have further problems to face. The three most important of these are those of preservation, protection and access. A vast number of our older volumes are in a very bad state of repair-some of the more important were re-bound in 1937, but many are still in a heart-breaking condition. The cost of binding is astronomical and it is unlikely that we will ever be able to afford to undertake a complete programme of this sort, but as a palliative measure we might be well advised to repair some of the less damaged volumes ourselves with adhesive tape. This is a practical step which falls short of perfection, but which might indeed save some of our volumes from a much worse state. The addresses in the metal box in the Young Room should also be bound, or at least placed in folders.
Allied to the problem of preservation is that of protection. Though untroubled by moth and rust we do have to contend with the awful ravages of dust, and I suspect that thieves break in. Even to-day books " walk" from our shelves and, though they may yet turn up, I am inclined to wonder where are our copies of Jenner, of Akenside's De Dysenteria inscribed " for Dr. Cullen from Dr. Hunter," or de Quincey's Opium Eater or Dover's Ancient Physician. These are treasures which are at present lost, and though they may have only strayed I fear it is more likely that they have been stolen. Most of our cases must perforce be locked, and with regard to the havoc already wrought by dust it is most desirable that they should be glass-or perspex-fronted. We have baulked at this latter problem before, but I feel that the time is now ripe for further investigation as to the cost of such a measure and we should give very serious consideration to ways and means. The locking of cases in turn raises the problem of access. Ideally any member should be at liberty to browse around the shelves. However, as past experience has shown this to be scarcely practicable, we must devise some scheme whereby books could be consulted at specified limes or whereby keys could be " signed out" for limited periods. This again is not an easy problem, but it should not be beyond our ingenuity to solve it satisfactorily.
Finally, how is the Library to expand? We have already seen that rapid expansion is not possible on our limited budget, and it is probably not even desirable.
We certainly should continue to build up our collection of Journals, and we should, perhaps, do more about filing pamphlets and reports, but we do constantly need new books of general medical interest and replacements for textbooks. The trickle of such books bought by the Society is a t the moment pitifully small. Some of our old members and friends (such as D r Douglas Guthrie) from time to time present us with books, but I should like humbly to suggest that present members when they are about to relinquish active membership of the Society might like to present a book to the Library as a m ark of their gratitude to the Society as a whole for the benefits they have obtained here-and if such presentation be m ade after consultation with the Library Committee as to present needs ic would be of all the more value to the Society.
In attem pting to give you some idea of the history and scope of our Library, and some of the problems which will face us in the future, I hope I have been able to show what a magnificent, but challenging heritage we have fallen heir to. In this Library we have our contacts with our own past and with the accum ulated wisdom of centuries. The responsibilities for preserving and m aintaining w hat is good and useful in this unique collection, while at the same time providing for intelligent expansion and progress, are grave, but we owe it to our predecessors and to our successors in this place to grasp the opportunity which now presents itself of consolidating and improving this most precious of our tangible assets-The Society's Library.
They a ll w a n t "Life," wrote M cNair Wilson, " interested John H unter to the exclusion of everything else, and he studied life as he had begun to see it-namely, as the supreme resistance to the blind forces which surrounded it and impinged upon it . . . Life, on this showing, was self protective." This "supreme resist ance" of life leads in health to longevity, in disease or after injury to survival; and therefore it is of peculiar interest to surgeons. It appears to depend on an urge for continuing life common to all tissues, and easily demonstrated for certain cells in the laboratory by examining the resistance offered by renal and hepatic cells to a sequence of injuries produced by chemicals (for example uranium nitrate and carbon tetrachloride). Tissues differ from one to another in the tenacity with which they cling to life, some giving up before others. This may be of importance in the practice of the future, as the population of this and other countries ages. According to the Government A ctuary's projection, provided the general mortality rate continues to decline and' the fertility rate remains about the same, between 1951 and 1979 the total population of this country may rise by 1 % to 52,250,000; the pensionable population may rise by 43% to 9,500,000, while the number of children may fall by about 4% to 10,500,000. Doctors (and incidentally hospital planners) will have to deal with and pro vide for more aged and ageing tissues and for fewer children; they will also be able to determine whether the tissues of children of the present generation, who are growing to be larger and who are maturing earlier than the children of 25 or 50 years ago, will in fact retain their "desire for life" to ages sufficient to project them into the pensionable groups (males over 65, females over 60), a possibility at present unresolved. A t all levels of animal life, the desire for life expresses itself in the possession of three forms of biological reserve-self-defence, self-repair, and self-adjustment.
As I intend to deal particularly with selfadjustment, I shall deal with self-defence and self-repair only briefly.

Self-defence
There are, of course, two contributory factors to self-defence: the general response, which is an immunological one, and the local response, which can also be examined by histological methods. Both these aspects can be investigated in the laboratory, for the general pattern of response in laboratory animals resembles that in man. What does vary is the efficacy of defence against the various forms of noxious stimulus; physical, chemical and bacterial. The possibility of differences in efficacy is present not only between laboratory animals and man (though they are not uniformly present), but also between the various species of laboratory animals. And more importantly, there may be such differences between human races. Thus the resistance of the peritoneal cavity of the African to pyogenic organisms is greater than that of the European or the Asian. This is obviously the kind of difference which will become of increasing importance as world distances are reduced by better and faster means of communication. It is already of great importance in prognosis for those who practise in multiracial societies.

Self-Repair
T he capacity to repair injured tissues and to regenerate lost tissues appears early in anim al life; it is found in those anim als whose constituent ceils increase in num ber after they first becom e individual. The capacity may be the expression of a physiological process necessary to replace the wear and tear of use in such epiblastic structures as skin and hair, and such m esoblastic structures as the cells of the liver and the pancreas, and those of the blood. T he capacity may be extended to the replacem ent of tissues lost or interrupted, which is called healing. In lower anim als, for exam ple in the lizard, a com plex structure such as a tail m ay be replaced not only in bulk b u t also in anatom ical structure. H igher anim als do not possess this useful capacity. In m an the m ost com plex repair is the restoration of the epithelial lining of the gut, which includes the restoration of glands appropriate to the segm ent of gut involved.
R epair in the covering epithelium , the skin, includes the nails but not hair or glands. It is curious that the only other epiblastic structure which has the capacity for self repair is peripheral nerve, because (to take a m otor nerve as an example) it is merely the interm ediate link in the function of m ovem ent, and neither the initiator of m ovem ents (the brain) nor their effector (the muscles) has the capacity to regenerate. In some m esoblastic structures in lower verte brates (the liver of the dog for exam ple) regeneration in bulk quickly occurs after rem oval of large parts of the organ. The rem oval m ust of course leave behind enough parenchym a to sustain life, but it is curious th at the organ should at once set about rebuilding parenchym a far in excess of physiological needs.
T he capacity to regenerate com plex tissues decreases as the evolutionary scale is ascended; and finally includes-because of its survival value-only the replacem ent of com m only injured tissues. All other losses are replaced by connective tissue during the process of healing. I doubt the desirability of attem pting to modify so fundam ental a process, especially since departures from norm al tim ing in the process of self-repair often lead to instability of the repair.
All these varieties of self-repair-physiological, replacem ent in form and replacem ent in bulk-can be studied in the laboratory, for in higher anim als including m an the prim ary structures-bone, muscle, and nerve tissue-are the same. It is of interest to recall the possibilities of repair indicated by Sir Jam es Paget in his fam ous Lectures on Surgical Pathology (3rd edition, 1870).
1. In tissues form ed entirely by nutrient repetition-blood, epithelia. 2. In tissues of lowest organization, or lowest chem ical characterconnective tissue, bone. 3. T he tissues inserted into other tissues, connecting them with other structures-nerve fibres, blood vessels. This classification m ight well be used today.

Self-Adjustment
T he capacity for self-adjustm ent is most im portant for survival in the anim al kingdom , and particularly so in m an. It comprises two different kinds of adjustm ent. In the one, the patient " m akes do" with w hat he has after some disease or injury has deprived him of completeness in some physiological function. A n exam ple of this type of adjustm ent are the trick m ovem ents possible after paralysis of certain peripheral nerves, as when in paralysis of the radial nerve extension of the wrist is partly carried out by strongly flexing the fingers and so tightening the extensor tendons.
In the other type of adjustm ent structures a n d viscera have to undertake to function under conditions im posed by the surgeon, fo r exam ple after the tran sp lan tatio n of m uscles from the preaxial to the p ostaxial aspect of the forearm to relieve rad ia l palsy, or after anastom osis of the jejunum to the stom ach in the operation of gastroenterostom y. In m any of the operations of surgery the success and even the safety of the procedures depend on the capacity of the hum an body for self-adjustm ent. W onderfully efficacious as this capacity usually is, it m ay often be im proved, and its final a tta in m ent of m axim um com petence hastened, by the judicious use of all the social, m ental and physical auxiliaries which a re collectively called rehabilitation.
1. T h e sim plest form of self-adjustm ent is seen after th e destruction or rem oval of one of paired organs such as the kidney. T he rem aining organ, although containing am ple parenchym a for physiological needs, usually enlarges a little, as if to provide a little biological reserve. A djustm ent to the loss of single organs is not possible. Som etim es the loss is fatal if not artificially com pensated (pancreas); som etim es it gives rise to profound changes in function of the m ost com plex description (pituitary).
2. Som etim es adjustm ent is possible in virtue of the excess of parenchym a in an organ or tissue, over w hat is the m inim um physiological req u ire m ent. T he body adjusts itself a t once to the loss of five or six hundred cubic centim etres of blood, as donors who give blood for transfusion well know. Such structures as the liver and the thyroid are con structed on such generous lines as alm ost to give the im pression th a t they are prepared to lose portions from disease o r from injury; it is difficult to associate this with any evolutionary process. O n the other hand it seem s a little odd th at although other structures should have plenty of sp are parenchym a, so im p o rtan t a structure as the pituitary gland should have little or none, which leaves it very vulnerable to disease.
3. Instead of using excess of parenchym a for m aking adjustm ents, the body m ay utilise the fact th at there is overlapping of function betw een organs. T hus after rem oval of one cerebral hem isphere, not all cerebral control is lost over the con tralateral side of the body; which helps to com pensate for the lack of self-repair in the central nervous system . T h e stom ach m ay be com pletely rem oved by the operation of total gastrectom y, after which the intestinal juices are capable of com pleting the digestion of food. C om pensations such as these are not possible when there is no overlapping of function, as in the case of the pituitary or the pancreas, which are the only sources of their secretions.
4. O ne of the m ost im p o rtan t self-adjustm ents m ade by the body is to som e extent a norm al physiological process; the m aintenance of the constant com position of the body fluids-the milieu interieur of C laude B ernard. T his com position is altered by a great variety of causes, ranging from the m etabolic disturbances which follow injuries (including operations) to the com plex alterations seen when the alim entary tract is obstructed. T he rapidity and com pleteness with w hich th e body can m ake these adjustm ents is m uch reduced by other factors to deal with w hich no com pletely satisfactory bodily m echanism s seem to have been evolved; extrem e fatigue, extrem e m alnutrition, the presence of " stress." and in cases of trau m a the presence of gross infection.

5.
A vast num ber of adjustments can be m ade which are related to the conduits of the hum an body. The simplest division of these is into channels to which there is an alternative, and channels which are single.
A lternative channels can be subdivided again. There are those which are provided by nature, and which are already in existence, such as the anastom osing arteries, veins, and lymphatics which may form a collateral circulation when the main vessels are blocked by injury or disease. There are "relief" alternative channels the result of disease, as when an infected distended gall-bladder ruptures into the neighbouring duodenum ; the anastomoses formed by these internal f istulae are seldom completely satisfactory from an engineering point of view, because of awkward and abnorm al differences of pressure in the hollow structures so joined, and the lack of accurate union of their respective epithelial linings. Finally, there are those m ade by the surgeon, to which the body must accustom itself-such as gastro enterostomy, or the deviation of the flow of urine into the bowel. Arrangem ents such as the latter may be only "one-way" affairs, for while urine-to-colon is an adjustable arrangem ent, faeces-to-urinary bladder is not.
When there is no alternative to a given conduit, the problem s posed to the body differ. When the passage is a m ere tube without m uscular walls, such as the A queduct of Sylvius, then the body is powerless. W hen the conduit has m uscular walls, the body uses for the necessary adjustm ent the capacity of plain muscle to hypertrophy, to ensure that an obstruction in the conduit will be at least tem porarily over come. This useful property of plain muscle was first noted by John H unter; the possibility of hypertrophy is also present in cardiac muscle (to overcome vascular resistance) and in striated muscle (to increase capacity for work).
Tubes such as each ureter and the alimentary canal are not pro vided with alternative routes. But when they are totally obstructed the technical problems they present are different. The ureter is straight and has not excess length, so that the upper and lower ends cannot be brought together after a piece of it has been removed. On the other hand the alimentary tract is mobile, and excessively long, and the surgeon can m ake abnorm al junctions between its proxim al and distal parts, to which the body has been proved by trial to be capable of self-adjustment.
These three biological reserves-the capacity for self-defence, the capacity for self-repair and the capacity for self-adjustm ent are essential for the continuance of the hum an race. When the surgeon intervenes, it m ust be to provide a solution which has not been elaborated by the body itself in the process of evolution. A nd he must always be careful rather to aid the efforts of the body itself than to attem pt to substitute his own. Prior to 1933, aetiological studies of hum an influenza yielded little precise inform ation. In 1938 Shope showed that swine influenza, the analagous disease of pigs, was caused by a bacterium (Haemophilus influenzae suis) and a virus, in symbiosis. Two years later, Smith et al reproduced the signs of influenza in ferrets by the intra nasal injection of bacteria free garglings from cases of human epidemic influenza. The suspected virus aetiology was thus confirmed. This classic WS strain of the virus, and all subsequently isolated, serologically related •= strains were collectively designated the " influenza A " group of viruses. A t least two other m ajor serological groups have since been identified and these have been designated "B" and "C " respectively. Epidemiological studies have indicated that epidemic influenza, in its widespread form, is caused by viruses of the A group. A m obilis in mobile relationship exists between the influenza A virus on the one hand and the hum an host population on the other. Always in nature the tendency is towards a balanced inter-relationship between living species. Disturbances in the balance between virus and host, due to gross changes in either, or less m arked in both, may result in epidemics. The extent and severity of the outbreak is proportional to the degree of imbalance.

THE CAUSATION AND SPREAD OF EPIDEMIC INFLUENZA
The effect of changes in the nature of the parasite is to increase the num ber of susceptible potential hosts without any necessary accompanying immological or physical change in the latter. A mass of information has been accumulated which confirms that the influenza A virus is capable of much variation. H irst (1952) absorbed rabbit immune sera with several heterologous strains of influenza A virus and was able to show that in the period 1933 to 1952, seven specific antigenic types established temporary prevalence. Burnet has since dem onstrated that finer antigenic differences may be detected almost annually, and that the process of antigenic change is therefore more continuous than H irst suggests. This heritable variation would appear to be the result of discontinuous m utation, essentially similar to gene mutations in higher forms. Soon after a new antigenic type arises, it becomes the dom inant form responsible for epidemics all over the world. The mass transform ation is the end result of selective survival and overgrowth of one m utant type. In H irst's series referred to above each m utation involved the appearance of a new antigenic component, which was added to the old antigenic pattern. In other words the immunity resulting from infection by an epidemic strain of influenza A virus, will be effective against all previously occuring epidemic strains, though not against further m utational changes, provided no back mutation occurs. Between 1933 and 1952 there had been no reversal to an earlier antigenic pattern. Evidence has, however, been produced which would suggest that in 1957 a back mutation may have occurred. M ulder, in the Netherlands, showed that persons alive in 1890 possessed type specific antibodies against the A /A sia n /5 7 strain, whereas the rest of the community did not. There may therefore be a reasonable premise for considering a long term cycle of antigenic variation of influenza A.
Mutation to a form of greater transmissability would also appear to be of importance in the initiation and spread of an influenza epidemic As yet this change is little understood, and little direct work has been done on the subject. The "O" phase of the virus is said to be more readily transmissable than the "D" phase. The significance of this fact is not clear.
The clinical manifestations of epidemic influenza are dependent on more factors than spread of infection. The nature of the observed variation in virulence of the influenza A virus has not been explained. Perry et al (1954) have postulated the existence of "virulent genes" which undergo spontaneous mutation to a state of increased or diminished virulence. This adaptation is probably a step-ladder like process with many inheritable intermediate grades. The results of animal experiments suggest that the more widespread an epidemic becomes, the more likely it is to assume lethal characteristics. This work is still largely of academic importance.
In summary, virus mutation facilitates the commencement of an epidemic by the production of novel antigenic types, against which immunity is decreased, minimal or absent, depending on the extent of the change. Variation in transmissability may be important in facilitating spread. Variation in virulence probably accounts for observed differences in severity of clinical symptoms and death rate.
The changes which take place in the nature of the influenza virus are well known, though inadequately understood. Too little attention has been paid to the changing nature of the host population. These changes are twofold-immunological and physiological.
Specific antiviral antibodies are important in protecting the host against influenza. Francis (1941) has found evidence that in immune persons, anti body is present in the secretions of the respiratory tract. Local tissue immunity would also seem to be significant, but is difficult to evaluate. These mechanisms are the result of previous encounter with the virus. Potential hosts are characterised by a low level of specific antibodies. Such hosts may arise by one of three mechanisms-birth, entry from a community in which influenza is unknown, or lastly, waning of previous immunity. Neutralising antiviral antibodies have been shown to undergo cyclical changes. High and low antibody levels have been correlated with reduced and increased susceptibility to infection.
Studies have shown that levels are highest after an epidemic. Moreover anti-influenzal antibody is type specific. Hence the slight protection afforded by a lowered antibody is further reduced due to the small degree of cross-immunity against a mutant epidemic strain.
The most important physiological factor concerned in epidemic influenza would appear to be the age structure of the population. This may be a direct physiological effect per ,se or it may act through the mediation of the immune response. In infancy the defence is poor. Infection occurs readily and there is little inflammatory response. Mortality is high. On the other hand the 6-12 year old group shows high resistance. In the 1918 pandemic the number of deaths in this age group was negligible. In young adult life there is apparently an increased susceptibility to epidemic infection. This was seen in the 1918-1919 pandemic. However, this susceptibility may be more apparent than real, since, in the active period of life, exposure to infection is more frequent.
After middle age, the resistance to infection becomes poor. This group shows a high morbidity and mortality in influenza epidemics. Experiments performed by Burnet and Beveridge suggest that the physiological resistance of the mature host is associated with the presence of increased quantities of pharmalogically active substances, producing inflammatory change. Epidemic influenza therefore will spread more rapidly, and produce the C A U SA T IO N A N D S PR E A D O F E P ID E M IC IN F L U E N Z A 23 highest mortality amongst the very old and the very young. Exceptions to this general rule have been tentatively explained in terms of increased exposure to infection.
In addition to the well-established effects of immunological status and age, certain non-specific factors seem to be involved in determining whether influenzal infection will take place. For instance, climatic factors may have an influence on the respiratory mucosa, predisposing to infection.
This may be brought about directly via the blood supply, or indirectly by a complex horm onal mechanism.
Having considered the factors predisposing the individual host to infection let us turn our attention to the spread of the influenza virus throughout the community. Epidemic influenza is a disease of civilisation.
A t the dawn of m an's life on this planet the social unit was a small group con sisting, at most, of a few families. There was little intercourse between the different groups. Under such conditions the evolution of the influenza virus as a specific hum an parasite would be difficult. Before an epidemic can occur it is necessary that the host should live under social conditions which adm it of large community aggregates. In this way the epidemic spread of a pathogen can occur. M odern civilisation has provided the large communities, and its forms of rapid transport can convey an infected person from one community to another in a few hours. In doing so the seeds of disease are spread far and wide. The epidemic will persist until an ecological climax state is established, with the restoration of equilibrium between host and parasite.
By analogy with other disease conditions three sources of infection are possible. These are the patient showing the disease, sub-clinical cases, and healthy carriers. The overt case of influenza remains infective for about five days and is probably of param ount importance in the spread of the disease.
Hirst (1947) has suggested that some cases are more significant than others in this respect.
He showed that it was usually necessary to incubate eggs with undiluted, filtered garglings from cases of influenza before lethal infection of the egg was produced. Occasionally, however, relatively enormous quantities of virus were present so that 01 ml. of gargling con tained 10° lethal egg doses. Infection therefore may be spread by a few highly infective individuals, rather than by the members of a group to an equal extent. Burnet et al (1940) m ade observations on laboratory staff, and patients, of a mental hospital. The num ber in each group developing clinical influenza was com pared with the num ber showing serological evidence of infection. This experiment served to dem onstrate that a symptomatic infection with influenza A virus can occur. Hosts suffering from sub-clinical infection may well be of im portance in the spread of the disease. The insidious nature of the danger may perhaps m ake them of greater importance than those with clinical infection.
It has never yet been ascertained whether or not the hum an host can act as a healthy carrier of influenza. Such a conception would be useful since it would offer a convenient explanation for the survival of the virus between epidemics. Burnet has suggested that the influenza virus might exist in pathologically altered celts around some chronic lesion in the respiratory tract. Thence it might be liberated in response to some non specific infection or environmental stimulus. No proof of this hypothesis yet exists.
Though little or no work has been done on the subject, it is logical to assume that the influenza virus is spread from source to potential host via 24 R E S M E D IC A the air. T he seasonal incidence of influenza suggests this, as does the rapidity of spread of an epidem ic. It is assum ed that the virus, once liberated from the dam aged respiratory tract epithelium , passes upw ards into the pharynx and is expelled via the saliva. Thence it reaches a new host in some ill-understood fashion.
In 1945 Duguid showed th at m ost of the droplets of saliva expelled by speaking, coughing or sneezing originate in the front of the m outh, few if any coming from the nose or throat. T he fate of these droplets depends on their size. T he larger droplets fall to the ground in one or two seconds. T he sm aller ones (under 0 . 1 mm. in diam eter) evaporate im m ediately leaving solid droplet nuclei. An average num ber of I0º droplet nuclei may be p ro duced by one sneeze. T hough workers have been unable to isolate m icro organism s from droplet nuclei, their possible im portance in the spread of epidem ic influenza is very real W hen larger droplets fall to the ground they evaporate and subsequent dust-raising activities may give rise to dustborne contam ination of the air.
It is possible th at transm ission of the influenza virus from donor to recipient may take place by prim ary (droplet nuclei) or secondary (dust borne) air contam ination. Spread by fomites or direct spraying, though possible, are less likely. This fascinating subject awaits full investigation before the relative im portance of the various possible m ethods of infection can be ascertained.
As yet there are vast gaps in ou r knowledge of epidem ic influenza. This is reflected in the fact that, so far, epidem ic outbreaks have been impossible to control. It may be, however, as S tuart-H arris has said, th a t the present era is the first phase in our efforts tow ards th at end. It is only through a better understanding of the biological variation of the influenza virus and its m eans of spread, th at the goal of prevention of epidem ic infection m ay be reached. T his article is an attem pt to present a few of the interesting facets of poliom yelitis. It certainly does not include all the im p o rtan t aspects; these can be found in any standard text-book. T here is evidence th a t poliom yelitis occurred in very early tim es; indeed, O sler in his T ex tb o o k of M edicine in the 1890's believes the first recorded case to be in the Bible-2 Sam uel, ch. 4, verse 4-"A nd Jo n a th a n , Saul's son, had a son th a t was lam e on his feet. H e was five years o ld when the tidings cam e of Saul a n d Jo n a th a n o u t of Jezreel, and his nurse took him up and fled: and it cam e to pass, as she m ade haste to flee, th a t he fell, and becam e lam e. A nd his nam e was M ephibosheth." It was com m on belief th a t this paralysis follow ed a m inor accident, and that it was cause and effect; this belief persisted until well into the nineteenth century. T hus M ephibosheth fell and becam e lam e at the age of five. W as he the first recorded case of poliom yelitis? O sier believes so.

YOUR MEDICAL BOOKSHOP
T h e first description of poliom yelitis as a distinct clinical entity was in 1789, by M ichael U nderw ood in " A T reatise on the Diseases of C hildren." T he first epidem ic was reported by Sir C harles Bell from St. H elena in 1836. In the first half of the nineteenth century, clinical cases of poliom yelitis were rare, and largely confined to infants, whilst epidem ics were conspicuous by their absence. I n the second half of the nineteenth century, epidem ics began to ap p e ar, as in Stockholm in 1887 and 1895. These were studied by M edin, and his nam e is contained in one of the synonym s of polio m yelitis-H eine-M edin's disease-H eine being an orthopaedic surgeon in G erm any in 1840. M edin, on an epidem iological basis, showed the probability of poliom yelitis being an infectious disease, but it was L andsteiner who, i n 1908, proved its infective nature conclusively by transm itting the disease to m onkeys. In the past forty years, vast am ounts of research have led to considerable increase in our know ledge of poliom yelitis.
T h e actual virus is m inute, 15-20 m illim icrons in diam eter, and is thus one of the sm allest viruses know n. It can be grow n by tissue culture from hum an specim ens. Im m unological typing resulted in a total of 600 distinct serological types, but fortunately, they fall into three m ajor im m unological g ro u p s : T ype 1 o r B runhilde T ype 2 or L ansing T ype 3 o r Leon Types 1 and 3 are responsible for m ost epidem ics. T ype 2 b u t rarely. T h e virus is w orld-w ide; poliom yelitis as a disease is w orld-w ide too. In an ou tb reak of poliom yelitis, a large proportion of the population is infected with the virus, but only a few develop poliom yelitis as a clinical disease. T his concept of high proportion of infection with very sm all p ro portion of clinical disease is fundam ental.
T h e virus can be recovered during epidem ics from a large proportion of " contacts" -especially from their faeces a n d nasopharyngeal secretions.

RES M ED IC A
Spread of infection is probably by carrier contam ination of food, and by food contam ination by flies.
T he incidence of infection is best studied from serum antibody levels. T he following facts stand o u t: 1. Newly born infants have some degree of immunity transm itted across the placenta. 2. Approxim ately 150 latent cases of poliomyelitis-though some authorities quote 1000--occur for every case of paralytic poliomyelitis. 3. In countries with poor standards of hygiene, infection occurs early in life, in a great proportion of the population, but the incidence of clinical poliomyelitis is low; i.e. the higher the standards of hygiene and civilisation, the higher the incidence of poliomyelitis. The explanation of this is that in less hygienic areas, early infection results in a good, lasting, immunity. 4. T he relationship with a g e : (a) incidence of infection increases with age; (b) incidence of paralysis increases with age; (c) the m ortality rises with the age at the time of the infection. The virus is presented to the person to be infected, either in food, or in "droplets." Spread in the body via the axons of peripheral nerves is not now believed to be the avenue of invasion. The present day opinion is that the virus enters the alim entary tract, passing from there to the blood stream ; this phase of viraemia occurs prior to the clinical signs of polio myelitis. Neutralising antibodies develop rapidly and become m aximal at at the time of the " m ajor" illness. This must bring the viraemia to a close, and also explains why the virus is so infrequently isolated after the paralysis has set in. The virus is regularly found in the central nervous system soon after the onset of symptoms, and there must take place in the central nervous system, the gravest battle between host and virus, a few hours or days after the viraemia has ended. The outcome of this battle determines the degree of paralysis.
Typically the illness is biphasic, the phases by custom termed the "m inor" and " m ajor" illnesses.
The m inor illness is a slight catarrhal upset, occurring in about 40% of paralytic cases a few days before the m ajor illness. It is often only recognised in retrospect. The minor phase is believed to coincide with the invasion of the blood stream by the virus. T he variety of clinical pictures of the m inor illness is trem endous, and no uniform diagnostic syndrom e is recognised.
There is often an interval of a few days between the m ajor and m inor illnesses in which the patient feels well.
The m ajor illness is usually easily recognised. It is abrupt in onset. The m ajor illness may not lead to paralysis, and the term non-paralytic m ajor poliomyelitis avoids ambiguity. Neither the severity of the symptoms a t the beginning of the m ajor illness, nor the changes in the cerebro-spinal fluid, make it possible to say which case will develop paralysis.
The physical exam ination should be planned to give the m aximum inform ation with the m inimum disturbance and fatigue to the patient. The patient should be observed carefully, noting the level of consciousness, the presence or absence of a squint, the respiratory rate, etc. T he mental state is im portant; poliomyelitis patients are usually fully conscious, and adult patients may become hysterical with the onset of respiratory difficulty. By looking at the airway, listening to the breath sounds, and observing the irregular and em barrassed efforts to breathe through a pool of mucus, respiratory distress may be discovered.
Respiratory failure may be recognised, provided the larynx is not affected, by getting the patient to count rapidly, observing how far he can count in one breath; 20 or more is norm al, but with paralysis and respiratory failure it may be less than 10.
There are certain factors which affect the vulnerability of the m otor nerve cells. The first of these is physical activity, and this must be considered from two angles, before the onset, and after the onset of the m ajor illness. Exercise before the onset of the m ajor illness does not have any clear-cut association with the degree of dam age to the anterior horn cells. Exercise after the onset of the m ajor illness, however, is extremely dangerous. The type of physical activity is closely related to the site of paralysis; e.g. running-low er lim b s: piano playing-fingers and hands. T he second factor is tonsillectomy; it was found in 1947 that many cases of bulbar polio myelitis occurred 7-30 days after the patient's tonsils and adenoids had been removed. The virus was probably present at the time of the operation. The third factor is that of inoculations. It was shown in 1950 th at polio myelitis following within one m onth of a prophylactic inoculation is liable to take the form of a paralysis of the limb injected. A lum in the diphtheria inoculations was especially incriminated; probably any intra-m uscular injection has a similar effect. The conclusion reached is that such factors may affect the segmental blood supply to the cord, interfering with the blood brain barrier, with the preferential settling of the virus in those segments.
Treatm ent of the m inor illness is symptomatic. It is most im probable that the label " polio" can be attached at this stage, and all th at is required is for the patient to be protected from undue fatigue.
Treatm ent of the m ajor illness can give rise to many problems. Physical activity is dangerous, and psychological rest must be ensured a t the earliest possible moment. Should the patient be kept at home or sent to hospital? There is no doubt that a journey to hospital may be frightening and exhausting just at the time when rest is essential. Under epidemic conditions the indiscriminate transfer of all suspected cases of poliomyelitis to hospital is probably undesirable, seriously overburdening the hospital staff. The decision to move the patient to hospital should be based on the patient's interests alone; the other members of the family have probably already been exposed to the virus, so that from that aspect, transfer is of no added value.
Isolation is generally practised, although the effectiveness of it in this disease has never been proved.
In considering the care of a patient with poliomyelitis, it should be appreciated that 80% of patients with acute poliomyelitis survive the acute phase however they are treated; their lives are never in danger. Unfortunately, however, an expert degree of supervision is required to recognise early the cases needing special measures. The prevention of dangerous complications should be the aim of every unit adm itting patients suffering from poliomyelitis, while the other aspects of treatm ent such as care of limb muscles is of secondary im portance in the acute phase.
In clear-cut cases, " lum bar puncture" gains very little, but if there is the slightest doubt in the diagnosis, it is an essential.
Nursing care plays a trem endous part in the m anagem ent of a case of poliomyelitis. The confidence and reassurance of an efficient nurse can go a long way to acquire the relaxation, both physical and mental, so valuable to the patient.
Passive movements of the limbs, with the muscles and joints being put through their full range, are the keystone in the management of the paralysed parts. This is to obviate the tendency of paralysed muscles to shorten.

RES M E D IC A
A fter the full extent of the paralysis becomes evident, the value of bed rest is slight. M uscle recovery takes place for at least six m onths, and this recovery is believed to be a hypertrophy and increased efficiency of the non-affected muscle fibres.
All the time, the patient must be led along, perhaps at times driven, by the physiotherapist, the doctor, the orthopaedic surgeon, and by his family and friends, all of whom have their p art to play. The psychological m ake-up of the patient needs as much attention as the physical state.
Education of the patient is very im portant, for with the defect in " braw n," "b rain" becomes of even greater im portance; the prolonged treatm ent of hopeless muscles should be avoided, if it is going to interfere with much more im portant m atters concerning the patient's future.
M uch is now known about poliom yelitis, b u t there is still a great deal to be learned before we can feel we know all about it. It will always be one of the most fascinating conditions a doctor can meet. To the casual observer, this new edition would seem to differ from its pre decessors only in a som ew hat m ore logical order, an additional 22 pages and an increase in price. Closer exam ination reveals, however, that a far m ore extensive revision has been undertaken, and that as m any sections, notably the gastric and renal tests, have been reduced, the am ount of new m aterial included is greater than the additional pages m ight suggest. Large increases are to be found in those sections devoted to water and electrolyte balance, to the steroid horm ones, and to the m etabolic abnorm alities, while the accounts of such subjects as electrophoretic fractionation, the histam ine stim ulation of gastric function and the intravenous glucose tolerance curves are m uch expanded.

Book Review C L IN IC A L C H E M IS T R Y IN P R A C T IC
In the m ethods appendix there have also been extensive changes, m uch of the m ore recondite m aterial having been replaced by m ore m odern and m ore simple alternatives. Of especial interest is the appearance of the Clinitest, Ictotest and other sim ilar proprietary m ethods now fully established, and the inclusion of paper chrom atography for the identification of specific sugars.
This is a book of which one's seniors speak well, and to one about to em bark upon his clinical work there can be little doubt that this new edition is a most desirable pre-requisite.

On the Linear Transmission of Disease (J. R. S c o t t )
This simple people [Chayma Indians] have an insuperable dislike to cohabit with any deformed woman. This is indeed common to most savage tribes in a state of N ature, which is a state of great equality. Unless a woman be well formed she is neglected and dies barren. In Europe and wherever artificial manners prevail, ugly and even deformed women marry. The cupid of commercial countries is not the cupid of Pastoral poets.
. . . He speaks too of a gentleman begetting a daughter with eyes and hair differently coloured from any of his children, his wife, or himself, and imagining this arose from his thinking (sub coitu) on a little brunette he had taken a fancy to. It might or might not be from this cause, but I have no idea that hanging the bridal bed with a pall, would tend in the least to produce a Negro child. The sight of a Negro footman might be added without danger; but their contact would be more effectual in changing the colour of a first born. Physiognomy is no doubt varied by causes operational on the mind at or about the time of conception or it may be on the senses, and it is between the Physiognomy of man in its varieties and the variety of colour in domesticated anim als that the analogy seems chiefly to exist.
On Typhus (R. F. Osborne) It is recommended by some to bleed from a large orifice in the erect posture or as near it as circumstances will allow "ad diliquium anim i." I m ust confess that if bleeding is to be perform ed I rank myself among this class-for of all things I think half measures the most abom inable. There may be cases that require them but they are comparatively few. . . . I conceive that bleeding performed in this way is one of the most powerful remedies that can be employed in the case of fever. It may be said really to induce a state of the system totally incom patible for the tissue with febrile action, and the quantity of blood lost is so trivial that it rather serves to ease the system of the burthen of its suppressed secretions than to induce that state of alleged debility which the antivenesectors cry out so much about.

* * *
Blisters-though objected to by a few, seem to meet with the approbation of the generality of Practitioners. It is not easy to say how they alleviate the symptoms for which they are employed. It is said by some to be by derivation, by others, by the fluid which they cause to be secreted, or by both of these ways-and it has even been attributed to the absorption of the cantharides, etc.
It is certain, however, I believe, that they so relieve in general the violent headache and other symptoms for which they are used. They are sometimes in desperate cases applied as general stimulants to rouse the vital principlesbut scarcely ever with success. I understand they have been recommended to be placed along the spinal cord to allay the inflammation which is supposed generally to affect its m embranes in cases of Typhus.
On Paralysis (J. Cochrane) Rubefacients, the most particular of which are sulphuric acid and nitric acids interblended with unctuous substances, am m onia, the essential oil of Turpentine, oil of Am ber, m ustard and Cantharides; seem to be more beneficial when frequently repeated and a m oderate stimulus kept up, than when by their long continuance they inflame the part.

On Exercise (A. G. M oller)
Speaking of the hypertrophy of muscle with great use . . . When in uncovering the sad relics of humanity in the hospitals and dissect ing rooms of Paris how well and how beautifully m arked do we trace in the French subject those well developed muscles the voluntary motion of which had once given such peculiar animation to the lively and facetious countenances of that intelligent people.
Exercise should also be moderate as to its general quantity, and this on account of the mind as well as the body. M oderate exercise invigorates and improves the mind and fits it for its proper offices. T o o much devotion to it, indeed to all bodily pleasure, weakens or debases both; and though Socrates disdained not to learn dancing to preserve his health, though the wise and learned queen of P alm yra delighted in the exercise of the chase, though the divine Plato from a " broad-shouldered wrestler" becam e a philosopher, it will perhaps generally be found that those entirely devoted to such pursuits are men of brutal disposition and incapable of purely mental excitements and enjoyments.
Exercises should be attended to as it influences the passions of the mind. Hence those exercises should be used which m oderately excite the better passions, and those avoided which call forth the worse. For this cause we must disapprove o f such exercises as Boxing, Fencing, and others which, however they may be attended with some advantages, are too likely to call forth the violent passions of anger, hatred and revenge. These passions are calculated to produce very bad effects on the bodily health as well as on the m oral and intellectual systems. T op ical injuries also and even sudden death are very likely to occur during these exercises, either by accident or in consequence of the excitation of those passions.

Enteritis (G. B. Waddell)
When the ulceration takes place in a rapid manner the intestines are sometimes perforated with holes so that their contents escape into the cavity

Opp-Greyfriars Bobby at George I V Bridge
OPERA OCCULTA 33 of the abdomen. . . . Dr Baillie remarks that he has seen a communication established in this manner between the Vagina and Rectum in the Female, and between the Bladder and Rectum of the Male, moreover he has observed that connections formed between the Kidney and Intestines, where this morbid state existed. This is a wise provision of nature, by which the purulent matter, that would otherwise have been evacuated into the general cavity of the abdomen, is conveyed off by a ready channel and thus the supervention of peritoneal inflammation which would shortly have destroyed life is prevented.
The Enteric Fever of the West Indies (W. Graham, m.d .) It may not be irrelevant to add very briefly to the necessity of keeping up the cuticular discharge which is so essentially conducive to a state of health in tropical climates, and in proportions as the pores are open is evinced the superiority of the system to resist the effects of augmented temperature; during violent exercise, or while pursuing a journey, it will be necessary to recruit the exhausted frame by frequent libations of a beverage more renovating and more potent than water. The safety of the practice is proved by the universal adoption of it by the inhabitants of the West Indies, who never experience any of the dreadful effects, which a late author so ingeniously ascribed to indulgence in the Sangaree bowl.