928 on our
Southerners. But, if
a
State
win, perhaps individual residents seem exciting.
can
can
try
an
action and
The
possibilities
bring too.
Letters
to
the Editor
READING HARVEY FOREIGN AID
The news that the supporters of the World Bank and of other international agencies are calling urgently for the Administration to restrain Congress from making savage cuts in foreign-aid programmes is not exactly surprising. The country has been hit by a depression, and there are no signs that inflation will abate, what with the steep increases in social-security payments, the prospect of a big rise in fuel costs, and a negative balance of payments (largely the result of stupendous oil cost increases). It is no wonder that many citizens, with an average income of about$12 000, are casting a wary eye on the large sums directly or indirectly paid by the taxpayer on one or other form of foreign aid-aid which often seems to be unwelcome or misused. Disillusionment with some of the international organisations that administer the aid seems widespread, and the withdrawal from the International Labour Organisation aroused remarkably little hostile comment from the public at large. The Administration may have to move quite smartly to salvage the foreign-aid programmes against what appears to be a good deal of public indifference, if not of actual disapproval. Perhaps most worrying are the implications of proposed cuts in agricultural production. A great deal of land is going out of production under Government programmes, and the farmers are taking other areas out of cultivation on the grounds that it is unprofitable to farm them at current prices. Though there are considerable cereal surpluses at present, these could very rapidly be dissipated if there were crop failures in other parts of the world, or we were to have such unfavourable growing weather as we had in 1974.
West
Germany CHECK ON DRUG PRICES
The highly competitive drug industry in West Germany has been shaken up in the last year or so by the existence of the Transparenz-telegramm, or Weisse Liste, as it is commonly known. This White List, which was first published at the beginning of 1977,’ provides a comparison of drug prices so that German doctors can choose the cheapest products to prescribe for their patients. A new and much expanded edition of the list has recently been brought out, which covers 600 drugs and drug combinations in more than 3700 proprietary preparations. Wide variations in price have been brought to light. For example, a day’s supply of allopurinol can cost DM 0-32 or 1.70, depending on the manufacturer and the package; similarly tolbutamide can cost 30 or 66 Pfennig a day. The White List also provides information on side-effects and interactions and on the therapeutic uses of the medicines covered. And the new edition now identifies the drugs which the World Health Organisation has designated as essential,2 and drugs which are likely to affect reactions and thus impair a person’s ability to drive or to do his job. According to a statement from the pharmaceutical industry’s trade association, the White List has already had a considerable effect on the drug market; manufacturers of the cheaper drugs have been able to increase their turnover (by up to 24%), while for the more expensive products there have been losses of up to 11%. Publication of the list is thus a valuable counter to the rising costs of health care in Germany. 1. See Lancet, 1977, 2. ibid. 1978, i, 423.
i, 590.
SIR,-As Thomas Beddoes said, "Abbreviators destroy knowledge"; and those who have abbreviated William Harvey’s achievement merely to the demonstration that the blood circulates have destroyed a great deal. As Whitteridge has so lucidly shown, he did much more than that. 1,2 Not only did he correctly the contraction of the heart and the cardiac cycle, reversing the previously held views in each case, but also describe
by discounting the whole apparatus of the Galenic system of spirits and questioning the belief in the innate heat of the heart, he lifted a great yoke of tradition from the necks of the next generation. And his innovatory use and description of the animal "model" has had a profound influence on biological science. So we should read our great scientists to see what they said, not what someone else tells us they said; and how they said it, and why, in what circumstances, and under what difficulties. Harvey conforms as closely as any to the Kuhnian prototype of the great revolutionary scientist,3 and those who say that he took one idea from Servetus and another from Fabricius, or perhaps the whole from Thomas Hariot, miss the point. It was Harvey, and none of these others, who effected the scientific revolution that opened the way for the development of modern medicine, and in particular for the science of cardiology, which was soon initiated by Lower (see his neglected masterpiece Tractatus de Corde) and further developed by Hales. The significance of Harvey’s work was quickly appreciated; the ideas were there, but the techniques were inadequate. Dr Dormandy (April 1, p. 708) compares, to their detriment, the writings of the great scientists of the past, with the work of the great artists. The artists’ work, he says, "is as relevant today as it was a hundred or three hundred years ago ..."But many artists today consider Tintoretto and Rembrandt to be irrelevant to modern art. Tom Wolfe has written entertainingly about them in his book The Painted Word. Many would hold that such are not artists; and if there really are any professional historians who treat the works of the great scientists of the past as "an avoidance-worthy embarrassment" perhaps they are not historians. Dormandy says that "A great work of art is never superseded because it can never be fully assimilated." The same is true of a great work of science; but one must know how to read it, just as one must know how to interpret a great painting. To the naive viewer Renaissance art is pretty but old-fashioned; to the initiate it contains a richness of meaning not found in modern works. If this is not "quaint antiquarian interest" then neither is the pleasure, the excitement, and the sense of personal contact with a great and lively mind that comes from reading Harvey, Hooke, or Hales. We do not read the works of the great scientists only for technical information, just as we do not go to Uccello only for the rules of perspective or to Rembrant only for chiaroscuro. Is Dormandy being entirely fair? In this age, when people are so used to "pictures" as the medium for visual communication, and medicine is learned almost from strip cartoons, should he not be comparing the writings of the great scientists with the writings of the great artists? How many artists today read Theophilus on gold leaf, Cennini on craftsmanship, or Alberti on architecture? Ghiberti, Bisticci, and Vasari give us anecdote, not art. Certainly Leonardo’s notebooks are still studied ; but by artists? And for very much more than quaint anti1. Whitteridge, G. William Harvey and the Circulation of the Blood. London, 1971. 2. Whitteridge, G. An Anatomical Disputation Concerning the Movement of the Heart and Blood in living creatures, by William Harvey. Oxford, 1976. 3. Kuhn, T. S. The Structure of Scientific Revolutions. Chicago, 1970.
929
quarian interest? If we read Delacroix it is for his diary, and Whistler for his wit. Ruskin writes superbly about the role of iron in art and in nature ("we cannot even blush without its help") though we do not go to him for physiology, but perhaps he hardly counts as a painter anyway. So I am not suggesting that we should continue to read the ancients only because in their writings we can find the first statements of so many of the beliefs that we hold today, such as tha matter is atomic, that the brain is a great gland, and that the substance that activates the muscles travels down the nerves. I cannot deny, though, the sense of pleasurable superiority that hindsight bestows. Had Arthur Keith carefully considered Harvey’s beautiful description of the temporal sequence of the cardiac contraction, the motion appearing to begin from the auricles and to extend to the ventricles, and his almost poetic account of the dying heart (all other parts being at rest and dead, the right auricle still beats) he might have found the sinoauricular node earlier, by design, rather than later by accident.4 Or if someone had read Lower on the effects on the venous return in the pregnant woman of "the pressure of the uterine mass on the vena cava and both iliacs in the pelvis" more perceptively, the supine hypotension syndrome might have been described much earlier, and we would have been spared the nonsensical theories about the peculiar susceptibility to anaathetics during pregnancy that my generation was taught, and many deaths. Dormandy likens a great work of science to the food at a banquet. If I might take up his analogy I would suggest that the attitude he describes-that only the immediately assimilable is important, an attitude that concentrates on the essence and rejects the fibre-is responsible for the cerebral diverticulosis that afflicts so many today. Of course, as for the appreciation of art, some preparation and guidance is necessary, but in Garrison we have our Gombrich, in Cumston our Clark, and our Panofsky in Pagel. Finally, a good reason for reading the works of the great scientists is that they have said it all before, and so much better. I would recommend to your readers Stillman Drake’s most apposite, eloquent, and informative introduction to his translation of Galileo’s astronomical discoveries, and will end with the following quotation: "If modern physicists care nothing for the works of Galileo, that is of taste and not merely of progress. Modern poets still read Homer, and modern philosophers Plato, not only because those works are excellently written but because they throw light upon the origins of poetry and philosophy-matters of special interest to poets and philosophers, and not without a certain value and attraction to the rest of us. Similarly the works of Galileo are well written, and throw light upon the origins of modern science; hence, even if few physicists are interested in them today, it does not necessarily follow that no one else ought to be."5 a matter
Now read on. Enfield District
Hospital,
Enfield, Middx. EN2 8LJ
DAVID ZUCK
CLONIDINE IN OPIATE WITHDRAWAL
SiR,—We have given clonidine 5 p.g/kg to five male opiate addicts after withdrawal of 15-50 mg chronic methadone treatment. They had been addicted to opiates for 6-10 years and on methadone for 6-60 months. All gave informed consent to the study which required a 2-day phased withdrawal from methadone before admission to the research unit and at least 36 h without opiates. All had signs of opiate withdrawal, and urine specimens showing residual methadone only. A nurse recorded objective signs of opiate withdrawal every 30 min from 8 A.M. while the patients were at bed rest. At 11 A.M. and 1 P.M. the patients were given clonidine or placebo in matching capsules. Neither the patient nor his nurse or physician knew the order of administration.
Withdrawal symptoms after clonidine
(C) and placebo (P).
The severity of opiate withdrawal increased during the baseline period. After clonidine, withdrawal signs rapidly disappeared (see figure). All patients reported dramatic relief of distress. Placebo had no effect. Four patients were offered clonidine alone on discharge. All chose it rather than methadone. The first patient studied also chose outpatient clonidine, but was given 5 mg methadone as well having previously been on 25 mg methadone daily. All patients took 5 g/kg clonidine orally twice daily for a week. The only complaint was occasional sleep difficulty, and there were no signs of withdrawal. All of these patients had made previous unsuccessful attempts to withdraw from methadone. So far the four patients treated with clonidine alone for a week after hospital discharge are opiate-free and doing well. We tried clonidine because of the possibility of a noradrenergic mechanism being responsible for opiate withdrawal, as suggested by studies on a major brain noradrenergic nucleus, the locus coeruleus, in monkeys. The effects of electrical or pharmacological activation of this nucleusl-4 were strikingly similar to those noted after opiate withdrawal. Both morphine and clonidine blocked the effects of activation of the locus cceruleus1,4 in primates, correlating with the time course of decreased 1. Gold, M. S., Redmond, D. E., Jr. Neuroscience, 1977, 3, 250 (abstr). 2. Redmond, D. E., Jr., Huang, Y. H., Gold, M. S. ibid. 1977, 3, 258. 3. Redmond, D. E., Jr., Huang, Y. H., Snyder, D. R., Maas, J. W. Brain Res.
1976, 116, 502. 4. Keith, A. An Autobiography; p. 258. London, 1950. 5. Drake, S. Discoveries and Opinions of Galileo. New York,
1957.
4. Redmond, D. E., Jr. in Animal Models in Psychiatry and by I. Hanin and E. Usdin); p. 293. Oxford, 1977.
Neurology (edited
Southerners. But, if
a
State
win, perhaps individual residents seem exciting.
can
can
try
an
action and
The
possibilities
bring too.
Letters
to
the Editor
READING HARVEY FOREIGN AID
The news that the supporters of the World Bank and of other international agencies are calling urgently for the Administration to restrain Congress from making savage cuts in foreign-aid programmes is not exactly surprising. The country has been hit by a depression, and there are no signs that inflation will abate, what with the steep increases in social-security payments, the prospect of a big rise in fuel costs, and a negative balance of payments (largely the result of stupendous oil cost increases). It is no wonder that many citizens, with an average income of about$12 000, are casting a wary eye on the large sums directly or indirectly paid by the taxpayer on one or other form of foreign aid-aid which often seems to be unwelcome or misused. Disillusionment with some of the international organisations that administer the aid seems widespread, and the withdrawal from the International Labour Organisation aroused remarkably little hostile comment from the public at large. The Administration may have to move quite smartly to salvage the foreign-aid programmes against what appears to be a good deal of public indifference, if not of actual disapproval. Perhaps most worrying are the implications of proposed cuts in agricultural production. A great deal of land is going out of production under Government programmes, and the farmers are taking other areas out of cultivation on the grounds that it is unprofitable to farm them at current prices. Though there are considerable cereal surpluses at present, these could very rapidly be dissipated if there were crop failures in other parts of the world, or we were to have such unfavourable growing weather as we had in 1974.
West
Germany CHECK ON DRUG PRICES
The highly competitive drug industry in West Germany has been shaken up in the last year or so by the existence of the Transparenz-telegramm, or Weisse Liste, as it is commonly known. This White List, which was first published at the beginning of 1977,’ provides a comparison of drug prices so that German doctors can choose the cheapest products to prescribe for their patients. A new and much expanded edition of the list has recently been brought out, which covers 600 drugs and drug combinations in more than 3700 proprietary preparations. Wide variations in price have been brought to light. For example, a day’s supply of allopurinol can cost DM 0-32 or 1.70, depending on the manufacturer and the package; similarly tolbutamide can cost 30 or 66 Pfennig a day. The White List also provides information on side-effects and interactions and on the therapeutic uses of the medicines covered. And the new edition now identifies the drugs which the World Health Organisation has designated as essential,2 and drugs which are likely to affect reactions and thus impair a person’s ability to drive or to do his job. According to a statement from the pharmaceutical industry’s trade association, the White List has already had a considerable effect on the drug market; manufacturers of the cheaper drugs have been able to increase their turnover (by up to 24%), while for the more expensive products there have been losses of up to 11%. Publication of the list is thus a valuable counter to the rising costs of health care in Germany. 1. See Lancet, 1977, 2. ibid. 1978, i, 423.
i, 590.
SIR,-As Thomas Beddoes said, "Abbreviators destroy knowledge"; and those who have abbreviated William Harvey’s achievement merely to the demonstration that the blood circulates have destroyed a great deal. As Whitteridge has so lucidly shown, he did much more than that. 1,2 Not only did he correctly the contraction of the heart and the cardiac cycle, reversing the previously held views in each case, but also describe
by discounting the whole apparatus of the Galenic system of spirits and questioning the belief in the innate heat of the heart, he lifted a great yoke of tradition from the necks of the next generation. And his innovatory use and description of the animal "model" has had a profound influence on biological science. So we should read our great scientists to see what they said, not what someone else tells us they said; and how they said it, and why, in what circumstances, and under what difficulties. Harvey conforms as closely as any to the Kuhnian prototype of the great revolutionary scientist,3 and those who say that he took one idea from Servetus and another from Fabricius, or perhaps the whole from Thomas Hariot, miss the point. It was Harvey, and none of these others, who effected the scientific revolution that opened the way for the development of modern medicine, and in particular for the science of cardiology, which was soon initiated by Lower (see his neglected masterpiece Tractatus de Corde) and further developed by Hales. The significance of Harvey’s work was quickly appreciated; the ideas were there, but the techniques were inadequate. Dr Dormandy (April 1, p. 708) compares, to their detriment, the writings of the great scientists of the past, with the work of the great artists. The artists’ work, he says, "is as relevant today as it was a hundred or three hundred years ago ..."But many artists today consider Tintoretto and Rembrandt to be irrelevant to modern art. Tom Wolfe has written entertainingly about them in his book The Painted Word. Many would hold that such are not artists; and if there really are any professional historians who treat the works of the great scientists of the past as "an avoidance-worthy embarrassment" perhaps they are not historians. Dormandy says that "A great work of art is never superseded because it can never be fully assimilated." The same is true of a great work of science; but one must know how to read it, just as one must know how to interpret a great painting. To the naive viewer Renaissance art is pretty but old-fashioned; to the initiate it contains a richness of meaning not found in modern works. If this is not "quaint antiquarian interest" then neither is the pleasure, the excitement, and the sense of personal contact with a great and lively mind that comes from reading Harvey, Hooke, or Hales. We do not read the works of the great scientists only for technical information, just as we do not go to Uccello only for the rules of perspective or to Rembrant only for chiaroscuro. Is Dormandy being entirely fair? In this age, when people are so used to "pictures" as the medium for visual communication, and medicine is learned almost from strip cartoons, should he not be comparing the writings of the great scientists with the writings of the great artists? How many artists today read Theophilus on gold leaf, Cennini on craftsmanship, or Alberti on architecture? Ghiberti, Bisticci, and Vasari give us anecdote, not art. Certainly Leonardo’s notebooks are still studied ; but by artists? And for very much more than quaint anti1. Whitteridge, G. William Harvey and the Circulation of the Blood. London, 1971. 2. Whitteridge, G. An Anatomical Disputation Concerning the Movement of the Heart and Blood in living creatures, by William Harvey. Oxford, 1976. 3. Kuhn, T. S. The Structure of Scientific Revolutions. Chicago, 1970.
929
quarian interest? If we read Delacroix it is for his diary, and Whistler for his wit. Ruskin writes superbly about the role of iron in art and in nature ("we cannot even blush without its help") though we do not go to him for physiology, but perhaps he hardly counts as a painter anyway. So I am not suggesting that we should continue to read the ancients only because in their writings we can find the first statements of so many of the beliefs that we hold today, such as tha matter is atomic, that the brain is a great gland, and that the substance that activates the muscles travels down the nerves. I cannot deny, though, the sense of pleasurable superiority that hindsight bestows. Had Arthur Keith carefully considered Harvey’s beautiful description of the temporal sequence of the cardiac contraction, the motion appearing to begin from the auricles and to extend to the ventricles, and his almost poetic account of the dying heart (all other parts being at rest and dead, the right auricle still beats) he might have found the sinoauricular node earlier, by design, rather than later by accident.4 Or if someone had read Lower on the effects on the venous return in the pregnant woman of "the pressure of the uterine mass on the vena cava and both iliacs in the pelvis" more perceptively, the supine hypotension syndrome might have been described much earlier, and we would have been spared the nonsensical theories about the peculiar susceptibility to anaathetics during pregnancy that my generation was taught, and many deaths. Dormandy likens a great work of science to the food at a banquet. If I might take up his analogy I would suggest that the attitude he describes-that only the immediately assimilable is important, an attitude that concentrates on the essence and rejects the fibre-is responsible for the cerebral diverticulosis that afflicts so many today. Of course, as for the appreciation of art, some preparation and guidance is necessary, but in Garrison we have our Gombrich, in Cumston our Clark, and our Panofsky in Pagel. Finally, a good reason for reading the works of the great scientists is that they have said it all before, and so much better. I would recommend to your readers Stillman Drake’s most apposite, eloquent, and informative introduction to his translation of Galileo’s astronomical discoveries, and will end with the following quotation: "If modern physicists care nothing for the works of Galileo, that is of taste and not merely of progress. Modern poets still read Homer, and modern philosophers Plato, not only because those works are excellently written but because they throw light upon the origins of poetry and philosophy-matters of special interest to poets and philosophers, and not without a certain value and attraction to the rest of us. Similarly the works of Galileo are well written, and throw light upon the origins of modern science; hence, even if few physicists are interested in them today, it does not necessarily follow that no one else ought to be."5 a matter
Now read on. Enfield District
Hospital,
Enfield, Middx. EN2 8LJ
DAVID ZUCK
CLONIDINE IN OPIATE WITHDRAWAL
SiR,—We have given clonidine 5 p.g/kg to five male opiate addicts after withdrawal of 15-50 mg chronic methadone treatment. They had been addicted to opiates for 6-10 years and on methadone for 6-60 months. All gave informed consent to the study which required a 2-day phased withdrawal from methadone before admission to the research unit and at least 36 h without opiates. All had signs of opiate withdrawal, and urine specimens showing residual methadone only. A nurse recorded objective signs of opiate withdrawal every 30 min from 8 A.M. while the patients were at bed rest. At 11 A.M. and 1 P.M. the patients were given clonidine or placebo in matching capsules. Neither the patient nor his nurse or physician knew the order of administration.
Withdrawal symptoms after clonidine
(C) and placebo (P).
The severity of opiate withdrawal increased during the baseline period. After clonidine, withdrawal signs rapidly disappeared (see figure). All patients reported dramatic relief of distress. Placebo had no effect. Four patients were offered clonidine alone on discharge. All chose it rather than methadone. The first patient studied also chose outpatient clonidine, but was given 5 mg methadone as well having previously been on 25 mg methadone daily. All patients took 5 g/kg clonidine orally twice daily for a week. The only complaint was occasional sleep difficulty, and there were no signs of withdrawal. All of these patients had made previous unsuccessful attempts to withdraw from methadone. So far the four patients treated with clonidine alone for a week after hospital discharge are opiate-free and doing well. We tried clonidine because of the possibility of a noradrenergic mechanism being responsible for opiate withdrawal, as suggested by studies on a major brain noradrenergic nucleus, the locus coeruleus, in monkeys. The effects of electrical or pharmacological activation of this nucleusl-4 were strikingly similar to those noted after opiate withdrawal. Both morphine and clonidine blocked the effects of activation of the locus cceruleus1,4 in primates, correlating with the time course of decreased 1. Gold, M. S., Redmond, D. E., Jr. Neuroscience, 1977, 3, 250 (abstr). 2. Redmond, D. E., Jr., Huang, Y. H., Gold, M. S. ibid. 1977, 3, 258. 3. Redmond, D. E., Jr., Huang, Y. H., Snyder, D. R., Maas, J. W. Brain Res.
1976, 116, 502. 4. Keith, A. An Autobiography; p. 258. London, 1950. 5. Drake, S. Discoveries and Opinions of Galileo. New York,
1957.
4. Redmond, D. E., Jr. in Animal Models in Psychiatry and by I. Hanin and E. Usdin); p. 293. Oxford, 1977.
Neurology (edited
