1163
much needed in view of the pressures to prescribe expensive new drugs and the temptation to waste other resources for which one does not directly pay-yet it is doubtful whether a year or two’s laboratory work is the best way to promote this faculty, especially when the work is undertaken reluctantly. Much better, surely, if the future doctor encountered competent clinical scientists in his student years, in a teaching hospital where they and the clinicians were working together in conditions of mutual respect-a concept not very different from that favoured by FLEXNER but still only : partly achieved in the United Kingdom. as OLIVER4 clinical in science is Yet, warns, danger of disappearing as a vocation: university and Medical Research Council units find incrèasing difficulty in attracting dedicated’ clinical workers to a career in medical research. The reason is not just lack of money. The biggest obstacle’lies in a conflict between the needs of the talented researcher and the changes taking place in clinical work and training in hospitals. At the most superficial level, the clinical scientist is unlikely to earn many units of medical time in addition to his basic week unless he performs extensive routine clinical duties which would be inimical to his research. A more serious problem has become apparent’ with the new programmes for higher medical training in Britain. In the intervals between complaining about Health Service bureaucracy, doctors have established their own formidable bureaucratic machinery of postgraduate training. The Joint Committee on Higher Medical Training has been set up to lay down guide(J.C.H.M.T.) lines for training in approved hospital posts, and eventually it will issue certificates of accreditation to those who have successfully completed their specialist training.7 The need for better supervision of medical training is clear enough, and the Joint Committee has explained how a clinical researchworker can survive in the system by obtaining experience (and a certificate) in general medicine or some recognised clinical specialty. However, research has rarely thrived on certificates of adequate training. The most fruitful research arises from the ability to cross the lines between existing specialties. The research-worker with his certificate duly stamped in nephrology is less likely to be productive than the talented individual who has pursued at will the application of immunology to renal disease or the metabolic and endocrinological aspects of renal hypertension. He may, of course, once he has the appropriate certificate (and a consultant post), decide to cross boundaries, but youth is no longer on his side. After a 5-year medical course, a preregistration year, 3 years’ general training, and 4 years’ higher medical training, the powers
THE LANCET Where Are All the Scientists
Going?
consultants are cultivated, charming and excellent physicians, occasionally distinguished contributors to scientific knowledge, but the system does not seek out, does not reward effort or achievement in a scientific direction. For the consultant, scientific distinction is a becoming decoration, it is not the breath of his nostrils." "The
English
able
men,
between clinical practice and medical science observed by ABRAHAM FLEXNERI at the beginning of this century, and so eloquently reported to his American audience, was not peculiar to that period. In an appendix to the report of the Royal Commission on Medical Education, F. G. YouNG2 recounted the long battle which began with the first moves to incorporate universitytrained scientists in the London teaching hospitals, then regarded by the clinicians as their exclusive domain. Thatbattle was partly decided with the establishment of strong preclinical departments and professorial clinical units, but it would be idle to pretend that no tensions now exist between the needs of science and the needs of clinical practice.
THE
Only
unsatisfactory relationship
years ago PAPPwoRTa3
asserting "teaching hospitals have tended to become dominated by doctors whose main, and even sometimes whose only, interest is research". Admittedly, few of those working in teaching hospitals agreed that the emphasis had swung so far in favour of the ten
was
that
scientific. And now, on both sides of the Atlantic, anxiety is being expressed for the future of the medical researcher.4.5 His lack of a clear identity and a definable career has become more evident with the decline of the talented amateur and the need for greater specialised knowledge and skill. But this is not merely a crisis of identity. Firstly, most medical students study medicine with a view to becoming practising doctors. Students with scientific aspirations tend to be channelled into basic science rather than medicine. Secondly, clinical research has earned itself a bad name: would-be consultants have felt themselves under pressure to produce research papers, and, as PAPPWORrH3 and PARKINSON6 (among others) have pointed out, the results are rarely of lasting value. Doctors may come away from their laboratory work with a more scientific attitude and thus better able to assess new developments in medicine-and such critical 1. Flexner, A. Medical Education in Europe. New York, 1912. 2. Royal Commission on Medical Education; appendix 14. H.M. Office, 1968. 3. Pappworth, M. H. Human Guinea Pigs; p. 10. London, 1967. 4. Oliver, M. F. Eur. J. clin. Invest. 1977, 7, 1. 5. Earley, L. E. J. clin. Invest. 1976, 57, 1660. 6. Parkinson, J. Lancet, 1955, i, 1013.
Stationery
7.
are
Joint Committee on Higher Medical Training, 2nd Report. Royal College of Physicians, London, 1975.
1164
accredited doctor is at a grave disadvantage compared with the basic scientistwhose only postgraduate certificate is a PH.D. This is a very dif ferent environment from that in which previous generations of medical investigators flourished; a
modern,Richard Bright for instance would have grave difficulties in surviving professional trainGiven the uncertainties implicit in all research, the small number of individuals who have a real talent for doing it, the scarcity of senior academic posts, and the insecurity of working in areas of research that may be deemed unrewarding and deprived of funds at governmental whim, it is not surprising that some academics are fearful for the future.’ One thing seems clear: if doctors have little industrial muscle (as the Prime Minister says), clinical investigators have none. The dividends from investing in clinical research are too remote. OLIVER suggests that an international bureau (funded, for instance, through the European Economic Community) could be set up to finance career investigator posts, and this would help to emphasise the international value of medical research. But money is not enough. We have to make sure that the environment is a congenial one. The young investigator must have a reasonable prospect of a successful career with a senior post (a chair or research-unit directorship) at the end of it. He cannot afford to be constantly looking back to make sure he meets the training criteria imposed by an external body or worrying that his research may be abruptly terminated. If such a career ’could be offered in clinical university and research units, there would be no shortage of clinical investigators. Clinical scientists may already draw some cheer from the free circulation of doctors within Europe, which expands their horizons and perhaps gives them an escape route from uncongenial environments.9 But they need more than this. Their contributions to medical science and to the, training of doctors are out of proportion to their small numbers, and they must be allowed to
ing.8
see a
future.
,
Culture-negative Endocarditis A
FEW cases
of endocarditis elude the
most
strenuous attempts to isolate organisms. Since the 1930s, most reports of infective endocarditis have included patients (up to 27%) in whom blood-cultures remained negative.I-3 The reported prevalence depends on criteria for diagnosis-CATESand CHRISTIE,2 in their 1951 study of endocarditis, initially included only culture-positive patients, but Peart, W. S. Medical Research is too Important to be left to the Researchers! Lecture at the Royal Institution, Oct. 18, 1973. 9. Van Ypersele de Strihou, C. Eur.J. clin. Invest. 1977, 7, 323. 1. Cherubin, C. E., Neu, H. C. Am. J. Med. 1971, 51, 83. 2. Cates, J. E., Christie, R. A. Q. Jl Med. 1951, 20, 93. 3. Lerner, P. I., Weinstein, L. New Engl. J. Med. 1966, 274, 323. 8.
recognising that the clinical diagnosis was not always confirmed by cultures, extended their criteria. What are the likely causes of failure to isolate organisms in a patient with endocarditis? In more than 80% of patients with subacute bacterial endocarditis (S.B.E.), organisms are isolated from the first blood-culture.2,4 Probably the bactersemia is persistent rather than intermittent in most patients,S and four blood-cultures, taken over 24-48 hours in a febrile patient, will usually establish the diagnosis-though additional cultures are advisable in patients who have received antibiotics. One theory has it that bacteria can become so sequestered within vegetations that they do not enter the bloodstream, and the longer clinical history often associated with culture-negative endoon
carditis favours this notion. However, embolism is common in culture-negative endocarditis (55% according to HAMPTON and HARRISON6) and might be expected to disseminate infective material. Postmortem culture and microscopy of homogenised valve tissue may not reveal bacteria,6 and some culture-negative cases possibly represent inactive "burned-out" infections. Previous antimicrobial therapy does not seem to be an important cause of failure to isolate organisms. HAMPTON and HARRISON6 noted, in a series in which 41% of cases were culture-negative, that two-thirds of the culture-negative patients had recently received antibiotics, as against half the culture-positive group-but this difference was not statistically significant. WERNER et al. reported isolation-rates of 97% and 91% for non-treated and treated groups. Fastidious organisms difficult to isolate by conventional methods account for some rare cases of endocarditis. They include Brucella spp., Bacteroides spp., Hcemophilus spp., Streptobacillus mon-
iliformis, carbon-dioxide dependent staphylococci, and Coxiella burnetii. There is little evidence to implicate viruses in human endocarditis, despite the predilection of certain viruses-notably, Coxsackie B-for myocardium and pericardium, though valvulitis has been produced experimentally with Coxsackie B4 in monkeys.7 L-forms have been described in both endocarditis and septicaemia8,9 and may be responsible for latency and subsequent reversion of classic forms. MATTMAN and MATTMAN9 claim that L-forms are common, but this is not the impression given by published reports en masse, perhaps because L-forms are hard to recognise. They have to be cultured in osmotically stable media, and repeated subculture may cause them to revert to the parent state. 4.
Rabinovitch, S., Evans, J., Smith, I. M., January, L. E. Ann. intern. Med.
5.
Werner, A. S., Cobbs, C. T., Kay, D.,
1965, 63, 185. et
al.
J.
Am. med. Ass.
1967, 202,
199. 6. Hampton, J. R., Harrison, M. J. G. Q. Jl Med. 1967, 36, 167. 7. De Pasquale, N. P., Burch, G. E., Sun, S. C., Hale, A. R.,
Mogabab, Am. J. Heart, 1966, 71, 678. 8. Neu, H. C., Goldreyer, B. Am. J. Med. 1968, 45, 784. 9. Mattman, L. H., Mattman, P. E. Archs intern. Med. 1965, 115, 315.
W. J.
much needed in view of the pressures to prescribe expensive new drugs and the temptation to waste other resources for which one does not directly pay-yet it is doubtful whether a year or two’s laboratory work is the best way to promote this faculty, especially when the work is undertaken reluctantly. Much better, surely, if the future doctor encountered competent clinical scientists in his student years, in a teaching hospital where they and the clinicians were working together in conditions of mutual respect-a concept not very different from that favoured by FLEXNER but still only : partly achieved in the United Kingdom. as OLIVER4 clinical in science is Yet, warns, danger of disappearing as a vocation: university and Medical Research Council units find incrèasing difficulty in attracting dedicated’ clinical workers to a career in medical research. The reason is not just lack of money. The biggest obstacle’lies in a conflict between the needs of the talented researcher and the changes taking place in clinical work and training in hospitals. At the most superficial level, the clinical scientist is unlikely to earn many units of medical time in addition to his basic week unless he performs extensive routine clinical duties which would be inimical to his research. A more serious problem has become apparent’ with the new programmes for higher medical training in Britain. In the intervals between complaining about Health Service bureaucracy, doctors have established their own formidable bureaucratic machinery of postgraduate training. The Joint Committee on Higher Medical Training has been set up to lay down guide(J.C.H.M.T.) lines for training in approved hospital posts, and eventually it will issue certificates of accreditation to those who have successfully completed their specialist training.7 The need for better supervision of medical training is clear enough, and the Joint Committee has explained how a clinical researchworker can survive in the system by obtaining experience (and a certificate) in general medicine or some recognised clinical specialty. However, research has rarely thrived on certificates of adequate training. The most fruitful research arises from the ability to cross the lines between existing specialties. The research-worker with his certificate duly stamped in nephrology is less likely to be productive than the talented individual who has pursued at will the application of immunology to renal disease or the metabolic and endocrinological aspects of renal hypertension. He may, of course, once he has the appropriate certificate (and a consultant post), decide to cross boundaries, but youth is no longer on his side. After a 5-year medical course, a preregistration year, 3 years’ general training, and 4 years’ higher medical training, the powers
THE LANCET Where Are All the Scientists
Going?
consultants are cultivated, charming and excellent physicians, occasionally distinguished contributors to scientific knowledge, but the system does not seek out, does not reward effort or achievement in a scientific direction. For the consultant, scientific distinction is a becoming decoration, it is not the breath of his nostrils." "The
English
able
men,
between clinical practice and medical science observed by ABRAHAM FLEXNERI at the beginning of this century, and so eloquently reported to his American audience, was not peculiar to that period. In an appendix to the report of the Royal Commission on Medical Education, F. G. YouNG2 recounted the long battle which began with the first moves to incorporate universitytrained scientists in the London teaching hospitals, then regarded by the clinicians as their exclusive domain. Thatbattle was partly decided with the establishment of strong preclinical departments and professorial clinical units, but it would be idle to pretend that no tensions now exist between the needs of science and the needs of clinical practice.
THE
Only
unsatisfactory relationship
years ago PAPPwoRTa3
asserting "teaching hospitals have tended to become dominated by doctors whose main, and even sometimes whose only, interest is research". Admittedly, few of those working in teaching hospitals agreed that the emphasis had swung so far in favour of the ten
was
that
scientific. And now, on both sides of the Atlantic, anxiety is being expressed for the future of the medical researcher.4.5 His lack of a clear identity and a definable career has become more evident with the decline of the talented amateur and the need for greater specialised knowledge and skill. But this is not merely a crisis of identity. Firstly, most medical students study medicine with a view to becoming practising doctors. Students with scientific aspirations tend to be channelled into basic science rather than medicine. Secondly, clinical research has earned itself a bad name: would-be consultants have felt themselves under pressure to produce research papers, and, as PAPPWORrH3 and PARKINSON6 (among others) have pointed out, the results are rarely of lasting value. Doctors may come away from their laboratory work with a more scientific attitude and thus better able to assess new developments in medicine-and such critical 1. Flexner, A. Medical Education in Europe. New York, 1912. 2. Royal Commission on Medical Education; appendix 14. H.M. Office, 1968. 3. Pappworth, M. H. Human Guinea Pigs; p. 10. London, 1967. 4. Oliver, M. F. Eur. J. clin. Invest. 1977, 7, 1. 5. Earley, L. E. J. clin. Invest. 1976, 57, 1660. 6. Parkinson, J. Lancet, 1955, i, 1013.
Stationery
7.
are
Joint Committee on Higher Medical Training, 2nd Report. Royal College of Physicians, London, 1975.
1164
accredited doctor is at a grave disadvantage compared with the basic scientistwhose only postgraduate certificate is a PH.D. This is a very dif ferent environment from that in which previous generations of medical investigators flourished; a
modern,Richard Bright for instance would have grave difficulties in surviving professional trainGiven the uncertainties implicit in all research, the small number of individuals who have a real talent for doing it, the scarcity of senior academic posts, and the insecurity of working in areas of research that may be deemed unrewarding and deprived of funds at governmental whim, it is not surprising that some academics are fearful for the future.’ One thing seems clear: if doctors have little industrial muscle (as the Prime Minister says), clinical investigators have none. The dividends from investing in clinical research are too remote. OLIVER suggests that an international bureau (funded, for instance, through the European Economic Community) could be set up to finance career investigator posts, and this would help to emphasise the international value of medical research. But money is not enough. We have to make sure that the environment is a congenial one. The young investigator must have a reasonable prospect of a successful career with a senior post (a chair or research-unit directorship) at the end of it. He cannot afford to be constantly looking back to make sure he meets the training criteria imposed by an external body or worrying that his research may be abruptly terminated. If such a career ’could be offered in clinical university and research units, there would be no shortage of clinical investigators. Clinical scientists may already draw some cheer from the free circulation of doctors within Europe, which expands their horizons and perhaps gives them an escape route from uncongenial environments.9 But they need more than this. Their contributions to medical science and to the, training of doctors are out of proportion to their small numbers, and they must be allowed to
ing.8
see a
future.
,
Culture-negative Endocarditis A
FEW cases
of endocarditis elude the
most
strenuous attempts to isolate organisms. Since the 1930s, most reports of infective endocarditis have included patients (up to 27%) in whom blood-cultures remained negative.I-3 The reported prevalence depends on criteria for diagnosis-CATESand CHRISTIE,2 in their 1951 study of endocarditis, initially included only culture-positive patients, but Peart, W. S. Medical Research is too Important to be left to the Researchers! Lecture at the Royal Institution, Oct. 18, 1973. 9. Van Ypersele de Strihou, C. Eur.J. clin. Invest. 1977, 7, 323. 1. Cherubin, C. E., Neu, H. C. Am. J. Med. 1971, 51, 83. 2. Cates, J. E., Christie, R. A. Q. Jl Med. 1951, 20, 93. 3. Lerner, P. I., Weinstein, L. New Engl. J. Med. 1966, 274, 323. 8.
recognising that the clinical diagnosis was not always confirmed by cultures, extended their criteria. What are the likely causes of failure to isolate organisms in a patient with endocarditis? In more than 80% of patients with subacute bacterial endocarditis (S.B.E.), organisms are isolated from the first blood-culture.2,4 Probably the bactersemia is persistent rather than intermittent in most patients,S and four blood-cultures, taken over 24-48 hours in a febrile patient, will usually establish the diagnosis-though additional cultures are advisable in patients who have received antibiotics. One theory has it that bacteria can become so sequestered within vegetations that they do not enter the bloodstream, and the longer clinical history often associated with culture-negative endoon
carditis favours this notion. However, embolism is common in culture-negative endocarditis (55% according to HAMPTON and HARRISON6) and might be expected to disseminate infective material. Postmortem culture and microscopy of homogenised valve tissue may not reveal bacteria,6 and some culture-negative cases possibly represent inactive "burned-out" infections. Previous antimicrobial therapy does not seem to be an important cause of failure to isolate organisms. HAMPTON and HARRISON6 noted, in a series in which 41% of cases were culture-negative, that two-thirds of the culture-negative patients had recently received antibiotics, as against half the culture-positive group-but this difference was not statistically significant. WERNER et al. reported isolation-rates of 97% and 91% for non-treated and treated groups. Fastidious organisms difficult to isolate by conventional methods account for some rare cases of endocarditis. They include Brucella spp., Bacteroides spp., Hcemophilus spp., Streptobacillus mon-
iliformis, carbon-dioxide dependent staphylococci, and Coxiella burnetii. There is little evidence to implicate viruses in human endocarditis, despite the predilection of certain viruses-notably, Coxsackie B-for myocardium and pericardium, though valvulitis has been produced experimentally with Coxsackie B4 in monkeys.7 L-forms have been described in both endocarditis and septicaemia8,9 and may be responsible for latency and subsequent reversion of classic forms. MATTMAN and MATTMAN9 claim that L-forms are common, but this is not the impression given by published reports en masse, perhaps because L-forms are hard to recognise. They have to be cultured in osmotically stable media, and repeated subculture may cause them to revert to the parent state. 4.
Rabinovitch, S., Evans, J., Smith, I. M., January, L. E. Ann. intern. Med.
5.
Werner, A. S., Cobbs, C. T., Kay, D.,
1965, 63, 185. et
al.
J.
Am. med. Ass.
1967, 202,
199. 6. Hampton, J. R., Harrison, M. J. G. Q. Jl Med. 1967, 36, 167. 7. De Pasquale, N. P., Burch, G. E., Sun, S. C., Hale, A. R.,
Mogabab, Am. J. Heart, 1966, 71, 678. 8. Neu, H. C., Goldreyer, B. Am. J. Med. 1968, 45, 784. 9. Mattman, L. H., Mattman, P. E. Archs intern. Med. 1965, 115, 315.
W. J.
