MIISCELLANEA

Rediscoveries

Christopher C Booth

Royal College ofPhysicians, LondonNW1 4LESir Christopher C Booth,FRCP, Harveian librarian

BrMed-J 1990;301:763-8

What is discovery? For many centuries it was thought to have its origins in the divine. It was considered, forthat it was no more than the revelation ofthe work ofan example, that the presence in certain botanical speciesAlmighty Creator, a view still held by some among the of'substances that might have beneficial effects was afaithful. Furthermore, until the'late Renaissance if reflection of the beneficence of a Creator who haddiscoveries conflicted with the clerical interpretation of liberally distributed plants with such qualitiesthe Divine Will as revealed in Holy Scripture then the throughout the world. Their discovery or rediscovery,discoverer might find himself having to abjure'his not necessarily by medical professionals, was to beviews, as did the aged Galileo when he knelt before achieved as a result of the use by mankind of thatthe Most Eminent and Most Reverend Cardinals intelligence that distinguished the greatest of God'sInquisitor-Generals in 1633 and promised to abandon creations from all other species. Similarly, the"the false opinion that the sun is the centre of the world widespread distribution of mineral waters, whoseand does not move and the earth is not the centre of the supposedly beneficial effects were for so long theworld and moves."' Nevertheless, his heretical mainstay of medical treatment, were a divine contri-views were subsequently sustained and, as they were bution to the welfare of mankind. Mercifully, unlikescientifically established, required no rediscovery but' bleeding and purging, taking the waters seems to haveconfirmation. William Harvey, whose own views on been for the most part a harmless pursuit, though nowthe circulation of the earth around the sun are not virtually outmoded. By contrast, the removal of evilknown to us, had the good fortune that nothing is said humours from the blood by venesection has an echo ofin the biblical record about the circulation ofthe blood, rediscovery in the current vogue for plasmapheresis,so that, unlike Galileo, he had to contend only with which is considered to remove evil immune complexesscientific detractors. His work, too, however, was an from the circulation; and purging is reflected inexample of a discovery so firmly based on the scientific the modern era by the fashion for fibre, whosemethod that it required neither confirmation nor consumption has been thought, like purging, torediscovery. remove all manner of evil influences from the colon.

Divine giftsHealing has always been associated in the popular

mind with the miraculous, and it is perhaps for thisreason that medical discovery was for so long thought

Frontispiece to "Dialogue on the two chief world systems" (1632) byGalileo. As a result of his views Galileo was brought before theInquisition on charges ofheresy

Revealed not createdMuch of scientific discovery has always, in fact, been

revelatory. The structure of DNA in the cells of themen who created the great cave paintings of Lascauxwas presumably no different from our own, and thecurrent surge towards the sequencing of the entirehuman genome will succeed in showing something thathas been present since long before the ancient Greeks,the authors of the hieroglyphic record, Alexander theGreat, or Julius Caesar. Whether scientific discoverycan be regarded as truly creative, as is often claimed byscientists, is uncertain, as it is axiomatic in science thatdiscoveries should be repeatable. Scientists may sharewith creative artists similar qualities of imagination,but the production ofa symphony by Beethoven, a playby Shakespeare, and a painting by Rembrandt areclearly unique events and can never be repeated by anyother- person. And if Bach's St Matthew Passionhad been destroyed in the years after his death, ascould well have happened, it would never havebeen recreated by Mendelssohn and his friends, whorediscovered the music in the nineteenth century. Bycontrast, much of scientific discovery, so wondrousa process to all who search out the secrets of nature,would, it has been claimed, be revealed sooner or laterregardless of individual brilliance. It is for this reasonthat priority occupies so central a position in thescientific mind. And it is for this reason too that thehistorical pathway of science, and ofmedical science inparticular, is paved both with discovery and withrediscovery.

Technological masterpiecesThe achievements of technology, however, must be

considered differently. They undoubtedly do requirecreative genius, but once discovered they are usually

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laking the waters at theRoom, Bath by HumphrRepton (1789)

Jenner's rediscoveryIn the history of biomedical science, however, there

are many examples of rediscovery. During the pastthree centuries much that came to belong to medicalscience was in fact a rediscovery of something alreadyexisting in the rich underworld of folk medicine. Theestablishment of digitalis as a cardiac drug in the

E<1 IhI E X 1780s owes everything to the recognition by WilliamWithering of its presence in a concoction for dropsyused by an elderly herb woman in -Shropshire. Simi-larly, the earliest methods for preventing smallpox

,;I; iIt: were known in many different parts of the worldlong before the established profession of medicinediscovered them.The first protective measure was thetechnique of inoculation, in which material was takenfrom a smallpox vesicle of an affficted person andinoculated into the skin. A mild and usually non-fatalattack of the disease would ensue, and thereafter therewas lifelong immunity. In Europe in the seventeenthcentury smallpox scabs could be rubbed into the skin,and this was done in areas as far apart as Wales, Poland,

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rey notforgotten and rarely neglected. The creation of the > -*steam engine and Arkwright's spinning jenny andthe techniques of radiography, computed axial Atomography, and nuclear magnetic resonance are allexamples of creative technology that has producedinventions that were not already in existence (as isthe human genome) waiting to be revealed but whichrequired the genius of unique people to create. ' 4 .

Furthermore, there is another important distinctionfrom science. Despite the popular view that thewheel is constantly being rediscovered, once a greattechnological advance has been made it rarely has to berediscovered and is usually put immediately to use.Gunpowder needed no rediscovery, nor did any of thegreat technological advances of our own era, whichinclude the internal combustion engine, poweredflight, instant communication throughout the globe,and all of the horrendous apparatus now availableto nations for the destruction of each other. Suchawesome achievements will not be rediscovered andthey have all been, used. Perhaps the only mIA jor -exception to this generahsation is the microscope, 'which for more than a century after Leeuwenhoek layscientifically unexploited. ..

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and southern Italy. In 1700 a paper to the Royal Societyin London described the Chinese method of inocula-tion, dating from antiquity, M which crust materialwas inserted into the nostrils. Yet so far as westemnEurope is concerned, the technique had to be re-discovered in 1718 in Constantinople by Lady MaryWortley Montagu, wife of the British Ambassador to

S3 ^ wTurkey, and it was she who introduced it into Britain.By the second half of the eighteenth century thetechnique was widely practised as a preventivemeasure in Britain.'There are those who argue that the replacement of

inoculation at the end of the eighteenth century byJenner's discovery of vaccination, published in 1798,was a rediscovery, for the idea that cowpox mightprevent smallpox was not new. In 1765 Fewster hadwritten- a paper entitled "Cowpox and its Ability toPrevent Smallpox." Four years later Bose in Germanycalled attention to the protection against smallpoxenjoyed by milkmaids, as was also well known to

William Withering (1741-99) learnt ofthe valuable effects ofdigitalis Jenner. Nash in 1781 suggested that the inoculation ofbecause ofits use in folk medicine cowpox might be preferable to smallpox inoculation as

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Benjamin Jesty (1737-1816) vaccinated with cowpox 24years beforejenner

Not the daily tot ofrum but limejuice, served on board the"Alert." The Royal Navy wasextremely slow to bring scurzyunder control

it was neither fatal nor infectious. Perhaps the mostimportant claim to have preceded Jenner was that ofthe Dorset farmer, Benjamin Jesty of Yetminster, whovaccinated both his wife and his two sons with cowpoxmaterial in 1774, 24 years before Jenner's publication.3There is no evidence that Jenner knew of theseattempts. Furthermore, although Jenner's techniquemay be classed historically as a rediscovery, he was theonly investigator of the beneficial effects of cowpoxinoculation to have followed up his vaccination withan attempt to inoculate smallpox in the traditionalTurkish manner and to show that he could no longerinfect his subjects. It was he, therefore, who quitejustly received the reward by parliament of £10 000 in1802 and £20 000 four years later, despite the claims ofothers.

Slow to catch onA further example of an eighteenth century medical

discoverv that was in fact a rediscovery was the

recognition that it was possible to prevent scurvyamong seamen. It was truly extraordinary that theRoyal Navy was so slow to find out how to deal with theravages of this often fatal disease. In the early years ofthe seventeenth century Captain James Lancaster ofthe East India Company had succeeded in preventingscurvy in his own ship by feeding bottled lemon juice tohis crew, whereas the crews of two ships that sailed incompany with him suffered severely. Woodall, inhis surgeon's log book, had recommended the useof lemon juice in 1617, yet when Admiral Ansoncircumnavigated the globe between 1740 and 1744 helost two thirds of his ship's company of 961 men, adeplorable experience that stimulated contemporaryphysicians and surgeons to inquire into the causesof scurvy. James Lind's pioneering clinical trial oforanges and lemons was carried out in the 50 gun shipHMS Salisbury in 1747, but despite his success inshowing the virtues of fresh fruit juice conservativeattitudes died hard in both the forecastle and in theAdmiralty. Not until nearly 50 years later, after theintroduction by Gilbert Blane of lime juice for allseamen in naval ships, was the disease brought undercontrol.4 Yet it is a measure of the hazards ofignorancethat Captain Scott and his colleagues were to sufferfrom scurvy during their ill fated journey to the SouthPole more than a century later.

If these examples of the influence of traditionalhealing seem to belong to the past it is well to recall thatthe introduction to Britain in 1955 of the rauwolfiaalkaloids for treating high blood pressure' was arediscovery of a remedy long known to Eastern,and particularly Indian, medicine.6 They remain ofmajor importance as therapeutic agents, particularly indeveloping countries.

Discovered before their timeRediscovery is a particular feature of the clinical

practice of medicine. The practice of naming diseasesafter those who supposedly first described them offersample evidence that observant clinicians faced withsimilar clinical problems will inevitably recognise thesame things. It is therefore hardly surprising thatvirtually no disease endowed with an eponym wasdescribed by only one person and that diseases areoften not described for the first time by the person withwhose name the disorder is popularly associated. Therecent recognition that the features ofCrohn's disease,apparently first published in 1932, were in factdescribed by Dalziel 20 years earlier provides aparticular contemporary example.7There are, however, many reasons why rediscovery

has been so much a part of biomedical science. Anoriginal discovery may be made long before itsimportance becomes apparent to other investigators.In addition, technical advances may be essential for thedevelopment of new ideas. The emergence of the ideathat a certain pressure in the blood is necessary toensure the adequate perfusion of different organsprovides a useful illustration. Stephen Hales carriedout his original experiments on the blood pressure ofthe mare in 1733. Nearly 100 years later Richard Brightdid not mention raised blood pressure as being of anyimportance in his patients who, retrospectively, maybe seen to have clearly died because of hypertension.He considered that the hypertrophy of the left ventriclethat he found was related to increased resistance in thecirculation, and the relation of high blood pressurewith human disease had to await a technical advance,the development of the sphygmomanometer.

Other more recent discoveries that were made beforetheir time include that of the giant axon of the squid. In1909 L W Williams published a work under theauspices of the American Museum of Natural History

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entitled The Anatomy of the Common Squid, LoligoPealii.' The journal Nature, reviewing the book,commented that "we did not expect very much in theway of novelty in a memoir of this kind, but the authoris to be congratulated on the important discovery of a

pair of giant nerve-cells situated in the pedal ganglionand each giving off a giant fibre."' According to theauthor it was the first time that such fibres had beendescribed in any mollusc. Nearly a quarter of a centurylater J Z Young again described the giant axons ofcephalopods in a communication to the PhysiologicalSociety.'" He went on to point out that they provided"very suitable material for study of living nerves."With Det Bronk, Ralph Gerard, and Keffer Hartline tohelp him at Wood's Hole and with the aid of amplifiersand loudspeakers he recorded the action potentialdischarge of a giant fibre of a squid after the applicationof a solution of sodium citrate to one end. As he sographically put it, "out came a buzzzzzzzzzz-one ofthe best sounds I have ever heard."" Cephalopod axonswere to prove of vital importance in studying basicmodels of neurophysiology and elucidating the natureof the nerve impulse.A more recent example of techniques apparently

emerging before their time is the polymerase chainreaction, which was discovered by Kary Mullin, HenryEhrlich, and their colleagues at the Cetus Corporationin California in 1985. As Nature has commented,molecular biologists might "like to dust off theJournalof Molecular Biology for 1971," in which H GobindKhorana and colleagues had previously suggested amethod for the "extensive synthesis of the duplexedtRNA genes" using similar techniques.'2 Nevertheless,it was not until the 1985 article that the now familiartechnique really took off.

Unsung heroesThe discovery and rediscovery of biologically

important proteins has been an increasingly importantfeature of modern biological science. The pressorproperties of renal extracts were first describedby Tigerstedt and Bergman in 1898'3 and werenot rediscovered and reclassified as renin until the1930s. Nowadays, many important proteins are beingdiscovered, rediscovered, and yet again rediscovered.This situation has arisen because of the remarkabletechnical advances in cell and molecular biology thathave permitted the isolation, sequencing, and cloningof particular substances. Groups working to trackdown the active principle in a particular biologicalprocess are quite likely to discover that the principle isin fact identical to one already known in a processpreviously thought to be unrelated.The capacity of modern scientists to forget what has

gone before is perhaps no greater than in any other fieldofhuman activity. Sir David Weatherall, however, haspointed out:

... modern molecular biology has forgotten classical genetics.If you were to read the now classical papers of David Botsteinwritten in 1980 about how one could use restriction lengthpolymorphisms to make a map of the human genome, youwould imagine that molecular biology had discovered linkage.However, the whole idea of mapping the human genome with

linkage markers was set out beautifully in 1927 by J B SHaldane in a marvellous essay called The Future ofBiology (SirDavid Weatherall, personal communication).

Haldane referred to the blood groups that "dividemankind into four classes," and he went on: "ifwe hadabout fifty. such characters . .. we could use them, by amethod worked out on flies by Morgan in New Yorkand his associates, as landmarks for the study of suchcharacters as musical ability, obesity and bad temper."He thought that such factors should enter into theconsiderations of those intending matrimony but was

equally doubtful that "the world will be converted intoa human stud farm."'4

Neglect of original workOther factors that may encourage the neglect

of original discoveries include publication in obscurejournals and in languages other than English. Further-more, recognition is more likely to go to those whowork in well known and internationally respectedinstitutions. The discovery of insulin by Banting andBest in Toronto in 1922 was the culmination of thework of a whole succession of investigators, includingLangerhans, the discoverer of the pancreatic islets, andall those who contributed to the finding that there wereboth external and internal secretions of the pancreas.There were also many who sought to use pancreaticextracts for the treatment of diabetes before Bantingand Best. Zuelzer treated a comatose diabetic patientwith pancreatic extract in Berlin in 1906 and E L Scottattempted to do the same in Chicago between 1911 and1912. But the person most forgotten in the storyof insulin was the Romanian, Nicolaus Paulesco,professor of physiology in Bucharest, who reportedspectacular decreases in the blood sugar concentrationof diabetic dogs after intravenous injections of his ownpancreatic extracts. He published his earliest findingsin 1920 in French, and further experiments were setout in four short papers published in Comptes Rendusde Science de la Societe de Biologie between April andJune 1921. Romanians have never forgiven theNobel prize committee for their apparently flagrantneglect of the work of their countryman, particularlyas Banting and Best, in their original communication,erroneously referred to Paulesco's findings as havingbeen "negative."'5There are other threats to the recognition of original

work. One of these is the blind acceptance ofauthority,which has bedevilled medical science since the time ofGalen. Modern medical science is not immune fromGalen-like figures, whose suppositions may havea pernicious influence on scientific opinion thateffectively hinders progress. The question, forexample, of whether absorption of substances acrossthe intestinal mucosa is an active process perplexedscientists at the end of the nineteenth century. Inthe early 1900s Weymouth Reid, working in therelative isolation of the department of physiology inSt Andrews University, Dundee, published a seriesof papers that provided compelling evidence thatintestinal transport is an active process. His work waslargely neglected, and in the 1930s it was the dogmaticviews of the Swiss physiologist, Verzar, that domi-nated contemporary thought. Verzar and McDougallpropounded the notion that absorption could beentirely explained on the basis of diffusion and osmosisand that active processes were not involved.'6 Theiropinions prevailed until the introduction of new invitro methods for showing active intestinal transport inthe 1950s.

Verzar's views also influenced the concept oflocalisation of absorption in the small intestine, whichif true would have provided important evidence infavour of active transport. As long ago as 1888

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1980s* 1981: The Centers for Disease Control

recognises AIDS* 1989: Identification of the cystic fibrosis

gene* 1989: Medical Research Council

announces funding for the humangenome mapping project

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Tappeiner had published data suggesting that theconjugated bile salts are selectively absorbed in theileum in the dog.'7 Verzar, sufficiently concerned bydata that conflicted with his cherished opinions,invited Frohlicher, one of his research assistants, torepeat Tappeiner's experiments. His observations

entirely supported Tappeiner's, but they weredismissed by Verzar. The concept that absorption inthe intestine might be localised was not accepted untilit was shown that the physiological absorption ofvitamin B-12 is a function of the ileum,'8 at least inspecies that are carnivorous or omnivorous. The

The Madhouse (1988)Sergei Chepik (b 1953; Russian)

Surprisingly, this picture, seen in Englandfor thefirst time lastyear, was painted by the Russian artist Sergei Chepik inthe 1980s, for his style seems to belong to an earlier era. Chepikwas born in Kiev in 1953 into an academicfamily in which thearts had an important role. His grandparents befriended manydistinguished artists and writers, including MikhailBulgakov, who was also a physician, who died in 1940. Itwas in this kind ofmilieu that Chepik spent hisformativeyears; his early trainingwas at the Kiev Institutefollowed by acourse at the Leningrad Academy, where he graduated in1979. Since 1989 he has lived permanently in Paris.

Until recently there was no such thing as artisticfreedom inthe Soviet Union. Avant-garde artists wereforced to gounderground and many starved. By the early 1930s Westernstyle experimentation was not tolerated-artists wereencouraged to celebrate thejoys ofcommunism in an officialstyle instituted by Stalin that was based on academic socialistrealism. Any work that offended the authorities was banned,and this is exactly what happened to Chepik's "Madhouse."In this picture he employs afigurative technique reminiscent ofFrench nineteenth century Romanticism, contrasting the

splendour ofthe decaying architecture with the grotesquepuppet-like figures. Could the badly damaged, almostunrecognisable image ofthe Virgin and Child be a reference tothe Virgin ofVladimir, the most holy icon in the RussianOrthodox Church? This powerful representation ofreligiousand political oppression won Chepik the gold medal at theSalon d'Automne in Paris in 1988 and a special medal inMonte Carlo in 1989. Not only is it an appropriate examplefor the last picture in this series, given the recent politicalchanges in eastern Europe, it also celebrates the splendid newsthat he is to have a one man show at the Roy Miles Gallery thismonth.

CLASSIC OF THE DECADE

1983: David Weatherall (ed). Oxford Textbook ofMedicine (two volumes). Oxford: OxfordUniversity Press.

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absorption of bile acids was then reinvestigatedand found to occur in the terminal ileum both inexperimental animals and in humans.

There is a further example from clinical gastro-enterology that illustrates how deeply held opinionsmay influence thought. In 1912 in Ceylon Manson-Bahr showed in a careful necropsy study that there wasatrophy of the small intestinal mucosa in a patient withintestinal malabsorption due to tropical sprue.9Manson-Bahr's observations were summarily dis-missed by the leading authorities of the day as merenecropsy artefact. That there are important patho-logical changes in the small intestine in patients withmalabsorption had to be rediscovered by Paulley in195320 and subsequently by those who pioneered theuse of jejunal biopsy techniques in the 1950s.2'

Deciding who got there firstIn our own era the pace of scientific advance has

accelerated dramatically. The potential rewards interms of fame, fortune, and an invitation to Stockholmhave also greatly increased the importance of priorityin medical science. As simultaneous technical advancesprovide so many contemporaries with similar scientificopportunities it is not surprising that the question ofpriority, of who discovered and who rediscovered,ranks so highly in the scientific consciousness. Therecent controversy between the French workers whooriginally discovered the virus that causes AIDS andinvestigators at the National Institutes of Health in theUnited States is a case in point. Although the source ofthe original discovery is not in doubt, it has requiredsome remarkable scientific journalism, which waspublished in a recent issue of the Chicago Tribune, togive the general reader an understanding of whodiscovered what and when.22 As the editor of thatnewspaper has written:It is a story of commitment and dedication to mankind and oftireless, often brilliant detective work within the magic andmarvellous world of medical technology. But it is also a storyof cut-throat competition and bare-knuckled politics, ofindividual ego and national pride, and of the kind of intensepressure on human beings that often brings out the worst ineven the best and can result in lying, cheating, and outrightfraud.

The pressures of the modern world on youngerresearch workers are particularly fierce. The scientificcommunity is sadly not immune from those who would

seek to advance their position by fabricating data, andthe question of fraud in science hangs heavily on thescientific achievements of our age.We need not wonder that rediscovery is so important

a feature of biology and medicine. After all, our entirescientific education is based on a process of repetitionof previous experimental work that is, when we first doexperiments, rediscovery. Furthermore, life itself is awhole process of rediscovery of what our forebearshave known-pain and pleasure, ecstasy and despair,beauty and ugliness. And for even the most modest ofthose who have had the privilege of working inbiomedical science there has been the rediscovery ofsomething that we can share even with Galileo-theexcitement of making a discovery.

I thank many friends and colleagues who have responded tomy inquiries about rediscoveries, in particular Dr Dai Rees,Sir Stanley Peart, Sir David Weatherall, Sir Colin Dollery, SirDouglas Black, and Dr Robin Weiss. I also particularly thankDr Tilli Tansey for drawing my attention to the work of L WWilliams on the giant axons of the squid.

1 Finocchario MA. The Galileo affair. Berkeley, Los Angeles, London:University of California Press, 1989.

2 Booth CC. The conquest of smallpox. Quart7 Med 1985;57:811-23.3 Dixon CW. Smallpox. London: Churchill, 1962:249-56.4 Ellis FP. Victuals and ventilation and the health and efficiency of seamen.

BrJ7Ind Med 1948;9:185-97.5 McGregor M, Segal N. The Rauwolfia alkaloids in the treatment of

hypertension. Br Heart 1955;17:391-6.6 Sen G, Bose KC. Rauwolfia serpentina, a new Indian drug for insanity and high

blood pressure. Indian Medical World 1931;2:194-201.7 Bannerjee AK, Peters TJ. The history of Crohn's disease. J R Coll Physicians

Lond 1989;23:121-4.8 Williams LW. The anatomy of the common squid, Loligo pealii. Leiden: Brill,

1909.9 Anonymous. The anatomy of the common squid, Loligo pealii [Review]. Nature

1910;83:366.10 Young JZ. Structure of the nerve fibres in Sepia. JPhysiol 1935;83:27-8P.11 Young JZ. Sources of discovery in neuroscience. In: Warden FG, Swazey JP,

Adelman G, eds. The neurosciences, paths of discovery. Cambridge: MITPress, 1975:18.

12 Anonymous. DNA amplification. Nature 1989;341:570.13 Tigerstedt R, Bergman PC. Niere und Kreislauf. Skandinavisches Archiv fur

Physiologie 1898;7-8:223-71.14 Haldane JBS. The future of biology. In: Possible worlds and other essays.

London: Chatto and Windus, 1927.15 Bliss M. The discovery of insulin. Edinburgh: Paul Harris, 1983.16 Verzar F, McDougall EJ. Absorption from the intestine. London: Longmans

Green, 1936.17 Tappeiner H. Cited in: Verzar F, McDougall EJ. Absorption from the intestine.

London: Longmans Green, 1936:218.18 Booth CC, Mollin DL. The site of absorption of vitamin B-12 in man. Lancet

1959;i: 18-21.19 Manson-Bahr PH. A report on researches in sprue in Ceylon, 1912-1914.

Cambridge: Cambridge University Press, 1915.20 Paulley JW. Observations on the aetiology of idiopathic steatorrhoea. BrMedJf

1954;ii: 1318.21 Shiner M. Jejunal biopsy tube. Lancet 1956;i: 17-9.22 Crewdson J. The great AIDS quest. Chicago Tribune 1989 Nov 19;section 5:

1-16.

World Medicine. A sort of obituary

continuedfrom page 762

downfall came because we were difficult to categoriseand couldn't explain to outside managers exactly whatwe were doing.

I see an ominous analogy between what happened toWorld Medicine at the start of the 1980s and what ishappening to the NHS at the start of the 1990s. In 1981we were taken over by a management that knew a lotabout the administration, production, and marketingof magazines yet failed to understand the transactionthat went on between us and our readers-the pub-

lishing equivalent of the doctor-patient relationship.When they replaced the editorial staff the publicationdied. Perhaps our creation carried within it the seeds ofits own destruction and, like Brunnhilde (that's thetrouble with Wagner, once you let him into an articlehe keeps coming back like a song), poor old WorldMedicine was destined to end by throwing itself uponthe flames.

Yet, while it lasted, it was a great place to be. I hopethat someone somewhere is dreaming up a successor,but please don't ask me how to do it. As they'd say inthe country where my genes were fashioned, if youknow what you're doing before you start you're neverlikely to begin.

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