- Email: [email protected]
ORPHAN DRUGS
290
explosive character of the outbreak and the fact that theepidemic area coincided with the water distribution system. However, campylobacters were not isolated from the water and an association between illness and water consumption was
not
demonstrated. A similar outbreak occurred in a strong association between illness
Vermont3 in 1978 and and
water consumption was reported, although campylobacters were not isolated from the water. Our report may therefore be the first in which both epidemiological and microbiological evidence has implicated the water-supply as
the vehicle of infection. The epidemiological evidence which implicates the unusual water supply to the school in this outbreak is summarised below. The outbreak was confined to the school staff and pupils. Milk supplied to the school was pasteurised and from a large dairy in a major town which also supplied the local village. The general practice in the village was responsible for the school pupils and therefore cases in the village were not likely to have been overlooked. The epidemic curve suggested several episodes, or continued contamination, ofavehicle widely distributed throughout the school. The survey of staff showed a strong association of illness and consumption of water from the main school building. Two water samples taken on June 1 from the storage tank yielded Campylobacter sp. of the same serotype as that obtained from patients in the school. Attack-rates of abdominal pain and/or diarrhoea amongst pupils were highest in those houses supplied solely from the clock tower tank, and lowest in those houses receiving little or no water from School House and which were also self-catering. Illnesses in pupils in this last group of houses could be explained by the relatively free movement of pupils within the school, and then either by their drinking water from a contaminated source or by person-to-person spread. One explanation for the lack of association between illness amongst pupils and the amount of water consumed is that the data from pupils were collected several weeks after the time of water contamination and are less reliable than data from the staff. Reported usual water consumption by pupils may have been based on consumption in the warmer weather at the end of term and not directly related to the time of the outbreak. However, the difference in reported water consumption at breakfast was only just below the conventional level of statistical significance and this difference suggests that the water-supply was more likely to contain infective doses of campylobacter early in the day. Failure to isolate campylobacter from water samples taken during a thorough and careful survey of the school watersupply only 3 days after the positive samples were taken is difficult to explain. Repeated sampling from the water supply over several weeks also did not produce campylobacters. However, the water was probably contaminated intermittently. Furthermore the extent of contamination may have been greater during the first part of the outbreak when the main peak of cases occurred and when all but one of the patients with severe symptoms became ill. The positive water samples were taken on the same day that the last pupil with gastroenteritis was admitted to the sanatorium. Subsequent milder cases may have been due to cross-infection in the school, although we could not find direct evidence of this. Since the water-supply was the most likely vehicle of infection, it is important to determine the point of contamination. The bore-hole is on the school site and does not drain local pasture. However, the supply is not chlorinated and is stored in an open-top tank. Chlorinated
from the village mains is added at irregular intervals. The storage tank itself is in a tower which on inspection showed evidence of roosting birds, and it is possible that faecal deposits from birds or bats were the source of infection.’ At the end of April, 1981, and around May 18 the clock tower area was used for the first time in many months to carry out work on the clock face, and it was reported that much debris and dust from the brickwork and rafters was dislodged. Our investigations indicate that faecal matter may have been dislodged with the debris and dust and that this could have been the origin of the outbreak. water
We thank Dr R. Pilsworth and Mr P. Maybury, P.H.L.S., Chelmsford and Dr I. Ash, medical officer for environmental health, Chelmsford and Mr W. G. Cockerell, Saffron Walden for their invaluable assistance in this investigation. REFERENCES 1. Robinson DA, Jones DM. Milk-borne campylobacter infection. Br Med J 1981; 282: 1374-76. 2. Mentzing L-O. Waterborne outbreak of campylobacter enteritis in Central Sweden. Lancet 1981; ii: 352-54. 3. Vogt RL, Fours HE, Varrett T, Feldman RA, Dickinson RJ, Witherell L. Campylobacter enteritis associated with contaminated water. Ann Intern Med 1982; 96: 292-96. 4. Gully PR. Medical Officers of Schools Association and Communicable Disease Surveillance Centre. Schools Reporting Systems. Paper read to the Royal Society of Medicine, Section of Epidemiology and Community Medicine, Feb. 12, 1981. 5. Robinson DA. Infective dose of Campylobacter Jejuni in milk. Br MedJ 1981; 282: 1584. 6. Knill MJ, Suckling WG, Pearson AD. Campylobacters from water. In: Newell DG, ed. Campylobacter; epidemiology, pathogenesis and biochemistry. Lancaster: MTP Press, 1982: 281-84. 7. Fenlon DR, Reid TMS, Porter IA. Birds as a source of campylobacter infections. In: Newell DG, ed. Campylobacter; epidemiology, pathogenesis and biochemistry. Lancaster: MTP Press, 1982: 261-62.
Occasional Book ORPHAN DRUGS IT is a sad irony that measures designed to protect patients from the ill-effects of new remedies have deprived some of them of the potential benefits of drug therapy; part of the price of improving drug safety has been paid by those with rare diseases. C. D. Leake, who said in 1929 "there is no short-cut from the chemical laboratory to the clinic except one that passes too close to the morgue", would certainly have welcomed the somewhat longer and safer path that was trod in the aftermath of the sulphanilamide disaster of 1937, but not perhaps the route mapped out in 1962 in the shadow of the thalidomide tragedy-a journey now so long and costly that few set out unless assured of rich rewards at their destination. Among those for whom the closing of Leake’s shortcut was to prove a mixed blessing were patients with uncommon disorders; their doctors, anxious to help the patients but continually frustrated by the consequences of well-meaning legislation, might well have reflected that the road to hell is paved with good intentions. Their problem was to find parents for their orphans-drugs that needed to be adopted, brought up, and sent into the world. In most countries pharmaceutical companies are commercial enterprises dedicated (not unreasonably) to the enrichment of their shareholders. This can best be done by marketing drugs for fairly common chronic disorders or for very common acute diseases. Drugs outside these categories have never been popular with the keepers of the balance sheets, but before 1962, when their cost, if not inconsiderable, was bearable, several remedies of limited or negligible commercial value were marketed as a service to medicine; and even if self-interest was not entirely lacking (a service drug improved the company’s public image and engendered goodwill) 1. Leake CD. The
pharmacologic evaluation of new drugs. JAMA 1929; 93:
1632.
291 the record of industry in this respect was commendable. But after 1962 compliance with the increasingly stringent requirements of regulatory agencies and insurance against claims relating to product liability put so high a price (possibly as much as$70 million by 1980 in the U.S.A.) on altruism and public relations that companies began to think twice or thrice before developing a drug that was unlikely to pay its way. To be a commercial winner a drug must be eligible for strong patent protection over a reasonable period of time and saleable in very large quantities in many countries. It is understandable if drugs that do not fulfil these criteria fail to reach the medicine cupboard. Although orphan drugs have it in common that they are for diseases that are rare (at least in the countries in which they are orphans) and unlikely to be profitable, they differ from each other in that some are untried compounds believed to have therapeutic potential; others have shown promise in limited clinical trials; and the ’remainder, while undoubtedly effective and already fully investigated and on sale elsewhere, remain orphans in some countries because the cost of meeting official requirements for marketing approval cannot be justified commercially. In his enlightening and important booksDr Fred E. Karch has gathered together the stories of M. H. Van Woert, S. L. De Felice, J. M. Walshe, J. F. Stubbins, T. H. Maren, L. 1. Goldberg, and J. F. Zaroslinski who have tried, with varying degrees of success, to find homes for the orphans L-5-hydroxytryptophan, carnitine, triethylene tetramine dihydrochloride, alkylating local anaesthetics, benzolamide, and dopamine. The tales are sagas of frustration; the repeated banging of heads against the brick walls of drug safety legislation, patent law technicalities, health insurance regulations, government buck-passing, and, above all, stark commercial reality. Fortunately, most of these stories had happy endings, but only because of the quite extraordinary tenacity of these men. It would be quite wrong, however, to suppose that since 1962 patients have been deprived of all important drugs of limited commercial value. In the U.S.A. new anticancer drugs and anticonvulsants have been developed and marketed by pharmaceutical companies collaborating with Governmentsponsored agencies in the National Cancer Institute Program and Antiepileptic Drug Development Program. The separate problem of treating rare parasitic diseases with well-established drugs not marketed in the U.S.A. has also been solved, albeit by benevolent skulduggery, by means of an ingenious if cumbersome bureaucratic device-the quaintly christened "compassionate investigative new drug licence"-for observing the letter if not the spirit of the law. However, not all orphan drugs can be adopted in these ways. What should be done? In the final chapter of Karch’s book, Louis Lasagna suggests some solutions: pharmaceutical companies might be given special tax allowances when investigating drugs of limited commercial potential; procedures for approval of new drugs by
regulatory agencies could be made less rigid, so that safety requirements might vary from drug to drug according to the rarity and severity of the disease for which the drug is to be used; a drug might be approved at an earlier stage than usual if restricted to use by specialist groups or institutions; and governments might accept responsibility for the financial consequences of injuries caused by unprofitable but essential drugs. Whether these measures will prove universally acceptable remains to be seen. But some progress has already been made. In the U.K., Government health departments and related agencies now help in the research and development of drugs for rare diseases and also hold (in the names of their Secretaries of State) the relevant clinical trial certificates and product licences, so relieving the drug manufacturer of much expense and of responsibility for druginduced damage suffered by patients; in the U.S.A. there are high hopes that legislation to solve the orphan drug problem will be passed by Congress this year. The orphans may yet find homes. Northern Regional Clinical Pharmacology Unit, Claremont Place, Newcastle upon Tyne 2. Karch FE, ed. Sw Fr 148.
Orphan drugs.
New
York,
D. M. DAVIES Basel: Marcel Dekker. 1982.
Pp. 210.
In
England Now
They keep on sending me Six Lucky Numbers, carefully randomised by their computer. About a year ago I was told that the computer had dropped a strong hint that something nice might shortly happen in the very street in which I live; but it didn’t. Sometimes, just to help them, I have solved a simple little problem involving four-leaved clovers or the Ace of Hearts, or even scraping an incrustation away with a coin. I always obey their injunction-Send No Money Now-strictly to the letter. How did I become involved in this game? I seem to remember that months and months ago I thought I needed a f6500 car, and this was the only way to get one. It was a mistake. I don’t really need a f6500 car. I can manage quite well without it. Mind you, I wouldn’t say no if one arrived unexpectedly outside my front door; but so far it hasn’t, and I have a hunch that it never will. How would I feel if one landed up in my next-door neighbour’s drive? Supreme indifference (I hope), apart from an upsurge of joy to find that the car really existed. Instead of cars I receive a spate of books that I would never dream of reading, and-would you believe it?-I am expected to pay for them! True, in mint condition they make impressive fodder for bring-and-buys and coffee mornings, where they go the rounds, each time aiding a different Good Cause. And now I have just discovered that my wife is also receiving batches of Six Lucky Numbers from some philanthropists with a f6500 car thay want to get rid of. They don’t pelt her with books but they urge her to stock up with those female garments I blush to name.
I am trying to work out whether or not this doubles our combined chances. What I can remember of the binomial theorem doesn’t seem to apply; so, just for the sake of argument, let us recklessly assume that our individual chances against getting a car are 10-minus one (Why the minus one? It looks more respectable that way). Do we add them together or multiply them? Meanwhile the Lucky Numbers continue to pour in. Is there any way of stopping them without hurting anybody’s feelings?
When last in Dublin, as a midwifery student, one of my friends asked for the Hamilton Advertiser. When told they had never heard of it, he asked if he could have a local paper instead. It was all a long time ago. We had travelled from post-war austerity Britain, with its ultility clothes, sparsely stocked stores, restrictions and rationing, to a city bursting with luxury consumer goods. These ranged from modern jewellery to old silver and from mouth watering confectionery to dry sherry. It was like an Aladdin’s cave. It was with pleasure, then, that I returned a few weeks ago to present a paper at a conference, held, to my delight, in the former rooms of that famous Irish surgeon and man of letters, Oliver St John Gogarty. The city did not seem to have changed at all. O’Connell Street and Grafton Street were still busy, bright, and bustling; the people garrulous and gregarious as ever; and I still could not get a seat for the Abbey Theatre. Perhaps there were a few more boutiques and coffee houses, but the pubs were much the same. I walked up to my old hospital at the top of O’Connell Street. The porter was kind and offered to fetch someone to show me round. But I did not stay long; there were too many ghosts. I would love to describe domiciliary midwifery in Dublin in those far off days but that would require a separate note. I shall always remember, however, the crowded tenement backrooms where, as a 20-year-old medical student, I brought babies into the world with all the confidence and ignorance of youth, helped only by Nature, a gas ring, and, thank heaven, someone’s grannie. Before I left, I went into a shop to buy my old hospital tie. It was produced readily and I mentioned to the draper that it had been over thirty years since last I purchased that particular tie. "Sure, sir," he said. "I hope you are in good health when you come back in thirty years’ time to buy another one."
explosive character of the outbreak and the fact that theepidemic area coincided with the water distribution system. However, campylobacters were not isolated from the water and an association between illness and water consumption was
not
demonstrated. A similar outbreak occurred in a strong association between illness
Vermont3 in 1978 and and
water consumption was reported, although campylobacters were not isolated from the water. Our report may therefore be the first in which both epidemiological and microbiological evidence has implicated the water-supply as
the vehicle of infection. The epidemiological evidence which implicates the unusual water supply to the school in this outbreak is summarised below. The outbreak was confined to the school staff and pupils. Milk supplied to the school was pasteurised and from a large dairy in a major town which also supplied the local village. The general practice in the village was responsible for the school pupils and therefore cases in the village were not likely to have been overlooked. The epidemic curve suggested several episodes, or continued contamination, ofavehicle widely distributed throughout the school. The survey of staff showed a strong association of illness and consumption of water from the main school building. Two water samples taken on June 1 from the storage tank yielded Campylobacter sp. of the same serotype as that obtained from patients in the school. Attack-rates of abdominal pain and/or diarrhoea amongst pupils were highest in those houses supplied solely from the clock tower tank, and lowest in those houses receiving little or no water from School House and which were also self-catering. Illnesses in pupils in this last group of houses could be explained by the relatively free movement of pupils within the school, and then either by their drinking water from a contaminated source or by person-to-person spread. One explanation for the lack of association between illness amongst pupils and the amount of water consumed is that the data from pupils were collected several weeks after the time of water contamination and are less reliable than data from the staff. Reported usual water consumption by pupils may have been based on consumption in the warmer weather at the end of term and not directly related to the time of the outbreak. However, the difference in reported water consumption at breakfast was only just below the conventional level of statistical significance and this difference suggests that the water-supply was more likely to contain infective doses of campylobacter early in the day. Failure to isolate campylobacter from water samples taken during a thorough and careful survey of the school watersupply only 3 days after the positive samples were taken is difficult to explain. Repeated sampling from the water supply over several weeks also did not produce campylobacters. However, the water was probably contaminated intermittently. Furthermore the extent of contamination may have been greater during the first part of the outbreak when the main peak of cases occurred and when all but one of the patients with severe symptoms became ill. The positive water samples were taken on the same day that the last pupil with gastroenteritis was admitted to the sanatorium. Subsequent milder cases may have been due to cross-infection in the school, although we could not find direct evidence of this. Since the water-supply was the most likely vehicle of infection, it is important to determine the point of contamination. The bore-hole is on the school site and does not drain local pasture. However, the supply is not chlorinated and is stored in an open-top tank. Chlorinated
from the village mains is added at irregular intervals. The storage tank itself is in a tower which on inspection showed evidence of roosting birds, and it is possible that faecal deposits from birds or bats were the source of infection.’ At the end of April, 1981, and around May 18 the clock tower area was used for the first time in many months to carry out work on the clock face, and it was reported that much debris and dust from the brickwork and rafters was dislodged. Our investigations indicate that faecal matter may have been dislodged with the debris and dust and that this could have been the origin of the outbreak. water
We thank Dr R. Pilsworth and Mr P. Maybury, P.H.L.S., Chelmsford and Dr I. Ash, medical officer for environmental health, Chelmsford and Mr W. G. Cockerell, Saffron Walden for their invaluable assistance in this investigation. REFERENCES 1. Robinson DA, Jones DM. Milk-borne campylobacter infection. Br Med J 1981; 282: 1374-76. 2. Mentzing L-O. Waterborne outbreak of campylobacter enteritis in Central Sweden. Lancet 1981; ii: 352-54. 3. Vogt RL, Fours HE, Varrett T, Feldman RA, Dickinson RJ, Witherell L. Campylobacter enteritis associated with contaminated water. Ann Intern Med 1982; 96: 292-96. 4. Gully PR. Medical Officers of Schools Association and Communicable Disease Surveillance Centre. Schools Reporting Systems. Paper read to the Royal Society of Medicine, Section of Epidemiology and Community Medicine, Feb. 12, 1981. 5. Robinson DA. Infective dose of Campylobacter Jejuni in milk. Br MedJ 1981; 282: 1584. 6. Knill MJ, Suckling WG, Pearson AD. Campylobacters from water. In: Newell DG, ed. Campylobacter; epidemiology, pathogenesis and biochemistry. Lancaster: MTP Press, 1982: 281-84. 7. Fenlon DR, Reid TMS, Porter IA. Birds as a source of campylobacter infections. In: Newell DG, ed. Campylobacter; epidemiology, pathogenesis and biochemistry. Lancaster: MTP Press, 1982: 261-62.
Occasional Book ORPHAN DRUGS IT is a sad irony that measures designed to protect patients from the ill-effects of new remedies have deprived some of them of the potential benefits of drug therapy; part of the price of improving drug safety has been paid by those with rare diseases. C. D. Leake, who said in 1929 "there is no short-cut from the chemical laboratory to the clinic except one that passes too close to the morgue", would certainly have welcomed the somewhat longer and safer path that was trod in the aftermath of the sulphanilamide disaster of 1937, but not perhaps the route mapped out in 1962 in the shadow of the thalidomide tragedy-a journey now so long and costly that few set out unless assured of rich rewards at their destination. Among those for whom the closing of Leake’s shortcut was to prove a mixed blessing were patients with uncommon disorders; their doctors, anxious to help the patients but continually frustrated by the consequences of well-meaning legislation, might well have reflected that the road to hell is paved with good intentions. Their problem was to find parents for their orphans-drugs that needed to be adopted, brought up, and sent into the world. In most countries pharmaceutical companies are commercial enterprises dedicated (not unreasonably) to the enrichment of their shareholders. This can best be done by marketing drugs for fairly common chronic disorders or for very common acute diseases. Drugs outside these categories have never been popular with the keepers of the balance sheets, but before 1962, when their cost, if not inconsiderable, was bearable, several remedies of limited or negligible commercial value were marketed as a service to medicine; and even if self-interest was not entirely lacking (a service drug improved the company’s public image and engendered goodwill) 1. Leake CD. The
pharmacologic evaluation of new drugs. JAMA 1929; 93:
1632.
291 the record of industry in this respect was commendable. But after 1962 compliance with the increasingly stringent requirements of regulatory agencies and insurance against claims relating to product liability put so high a price (possibly as much as$70 million by 1980 in the U.S.A.) on altruism and public relations that companies began to think twice or thrice before developing a drug that was unlikely to pay its way. To be a commercial winner a drug must be eligible for strong patent protection over a reasonable period of time and saleable in very large quantities in many countries. It is understandable if drugs that do not fulfil these criteria fail to reach the medicine cupboard. Although orphan drugs have it in common that they are for diseases that are rare (at least in the countries in which they are orphans) and unlikely to be profitable, they differ from each other in that some are untried compounds believed to have therapeutic potential; others have shown promise in limited clinical trials; and the ’remainder, while undoubtedly effective and already fully investigated and on sale elsewhere, remain orphans in some countries because the cost of meeting official requirements for marketing approval cannot be justified commercially. In his enlightening and important booksDr Fred E. Karch has gathered together the stories of M. H. Van Woert, S. L. De Felice, J. M. Walshe, J. F. Stubbins, T. H. Maren, L. 1. Goldberg, and J. F. Zaroslinski who have tried, with varying degrees of success, to find homes for the orphans L-5-hydroxytryptophan, carnitine, triethylene tetramine dihydrochloride, alkylating local anaesthetics, benzolamide, and dopamine. The tales are sagas of frustration; the repeated banging of heads against the brick walls of drug safety legislation, patent law technicalities, health insurance regulations, government buck-passing, and, above all, stark commercial reality. Fortunately, most of these stories had happy endings, but only because of the quite extraordinary tenacity of these men. It would be quite wrong, however, to suppose that since 1962 patients have been deprived of all important drugs of limited commercial value. In the U.S.A. new anticancer drugs and anticonvulsants have been developed and marketed by pharmaceutical companies collaborating with Governmentsponsored agencies in the National Cancer Institute Program and Antiepileptic Drug Development Program. The separate problem of treating rare parasitic diseases with well-established drugs not marketed in the U.S.A. has also been solved, albeit by benevolent skulduggery, by means of an ingenious if cumbersome bureaucratic device-the quaintly christened "compassionate investigative new drug licence"-for observing the letter if not the spirit of the law. However, not all orphan drugs can be adopted in these ways. What should be done? In the final chapter of Karch’s book, Louis Lasagna suggests some solutions: pharmaceutical companies might be given special tax allowances when investigating drugs of limited commercial potential; procedures for approval of new drugs by
regulatory agencies could be made less rigid, so that safety requirements might vary from drug to drug according to the rarity and severity of the disease for which the drug is to be used; a drug might be approved at an earlier stage than usual if restricted to use by specialist groups or institutions; and governments might accept responsibility for the financial consequences of injuries caused by unprofitable but essential drugs. Whether these measures will prove universally acceptable remains to be seen. But some progress has already been made. In the U.K., Government health departments and related agencies now help in the research and development of drugs for rare diseases and also hold (in the names of their Secretaries of State) the relevant clinical trial certificates and product licences, so relieving the drug manufacturer of much expense and of responsibility for druginduced damage suffered by patients; in the U.S.A. there are high hopes that legislation to solve the orphan drug problem will be passed by Congress this year. The orphans may yet find homes. Northern Regional Clinical Pharmacology Unit, Claremont Place, Newcastle upon Tyne 2. Karch FE, ed. Sw Fr 148.
Orphan drugs.
New
York,
D. M. DAVIES Basel: Marcel Dekker. 1982.
Pp. 210.
In
England Now
They keep on sending me Six Lucky Numbers, carefully randomised by their computer. About a year ago I was told that the computer had dropped a strong hint that something nice might shortly happen in the very street in which I live; but it didn’t. Sometimes, just to help them, I have solved a simple little problem involving four-leaved clovers or the Ace of Hearts, or even scraping an incrustation away with a coin. I always obey their injunction-Send No Money Now-strictly to the letter. How did I become involved in this game? I seem to remember that months and months ago I thought I needed a f6500 car, and this was the only way to get one. It was a mistake. I don’t really need a f6500 car. I can manage quite well without it. Mind you, I wouldn’t say no if one arrived unexpectedly outside my front door; but so far it hasn’t, and I have a hunch that it never will. How would I feel if one landed up in my next-door neighbour’s drive? Supreme indifference (I hope), apart from an upsurge of joy to find that the car really existed. Instead of cars I receive a spate of books that I would never dream of reading, and-would you believe it?-I am expected to pay for them! True, in mint condition they make impressive fodder for bring-and-buys and coffee mornings, where they go the rounds, each time aiding a different Good Cause. And now I have just discovered that my wife is also receiving batches of Six Lucky Numbers from some philanthropists with a f6500 car thay want to get rid of. They don’t pelt her with books but they urge her to stock up with those female garments I blush to name.
I am trying to work out whether or not this doubles our combined chances. What I can remember of the binomial theorem doesn’t seem to apply; so, just for the sake of argument, let us recklessly assume that our individual chances against getting a car are 10-minus one (Why the minus one? It looks more respectable that way). Do we add them together or multiply them? Meanwhile the Lucky Numbers continue to pour in. Is there any way of stopping them without hurting anybody’s feelings?
When last in Dublin, as a midwifery student, one of my friends asked for the Hamilton Advertiser. When told they had never heard of it, he asked if he could have a local paper instead. It was all a long time ago. We had travelled from post-war austerity Britain, with its ultility clothes, sparsely stocked stores, restrictions and rationing, to a city bursting with luxury consumer goods. These ranged from modern jewellery to old silver and from mouth watering confectionery to dry sherry. It was like an Aladdin’s cave. It was with pleasure, then, that I returned a few weeks ago to present a paper at a conference, held, to my delight, in the former rooms of that famous Irish surgeon and man of letters, Oliver St John Gogarty. The city did not seem to have changed at all. O’Connell Street and Grafton Street were still busy, bright, and bustling; the people garrulous and gregarious as ever; and I still could not get a seat for the Abbey Theatre. Perhaps there were a few more boutiques and coffee houses, but the pubs were much the same. I walked up to my old hospital at the top of O’Connell Street. The porter was kind and offered to fetch someone to show me round. But I did not stay long; there were too many ghosts. I would love to describe domiciliary midwifery in Dublin in those far off days but that would require a separate note. I shall always remember, however, the crowded tenement backrooms where, as a 20-year-old medical student, I brought babies into the world with all the confidence and ignorance of youth, helped only by Nature, a gas ring, and, thank heaven, someone’s grannie. Before I left, I went into a shop to buy my old hospital tie. It was produced readily and I mentioned to the draper that it had been over thirty years since last I purchased that particular tie. "Sure, sir," he said. "I hope you are in good health when you come back in thirty years’ time to buy another one."