The Rise and Fall of Modern Medicine (62 page)

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Benzodiazepines

The fourth pillar of the pharmacological revolution in post-war psychiatry was formed by the benzodiazepines, of which Valium (diazepam) is the best known. These are known as the ‘minor' tranquillisers, to distinguish them from the ‘major' ones such as chlorpromazine, so effective in controlling the agitation associated with schizophrenia. Symptoms of ‘minor' anxiety are a common reason for seeking medical attention and the extraordinary success of benzodiazepines, leading to their massive overprescription in the 1960s and 1970s, lay in the fact that, unlike the barbiturates that they superseded, they did not have a strong sedative action and were very safe. They could thus be prescribed with impunity for the ubiquitous mild psychological symptoms that people brought to the surgery.
13

These, the commercially most successful drugs of all time, only narrowly avoided not being discovered. Inspired by the success of chlorpromazine, Leo Sternbach of Hoffmann La Roche decided to try and find a completely new type of tranquilliser and began with a class of compounds which he had synthesised twenty years earlier as part of his postdoctoral studies at the University of Cracow in Poland. He synthesised compounds structurally related to the antihistamine group of drugs from which chlorpromazine had been derived, none of which had any special tranquillising effect. In 1957 it was decided to close down the research programme:

The laboratory benches were covered with dishes containing crystalline samples . . . the working area had shrunk almost to zero and a major clean-up operation was in order. My coworker, Earl Reeder, drew my attention to a few hundred
milligrams of two products which had not been submitted for pharmacological testing at the time so we submitted them for pharmacological evaluation. We thought the expected negative result would complete our work . . . Little did we know that this was the start of a programme which would keep us busy for many years.
14

After a few days Sternbach was rung by his pharmacologist to be informed ‘that the compound possessed unusually interesting properties in the tests for the preliminary screening of tranquillisers'. This last-minute discovery generated much excitement and raised the question why only this drug seemed to work as a tranquilliser. Its structure was duly reanalysed and turned out to be not what had been anticipated. Rather, while sitting on the bench it had been transformed into an entirely different type of chemical altogether – a benzodiazepine. Its precise mode of action remained unclear for a further twenty years until 1977, when benzodiazepine receptors were found in the brain which, it is thought, influenced the action of the neurotransmitter GABA.
15

The Slow Death of Psychoanalysis

John Cade, in giving his patient Mr W. B. his first dose of lithium salts, signed the death warrant of psychoanalysis, though he would scarcely have appreciated it at the time. Clearly the fact that a naturally occurring salt can, within a couple of weeks, terminate a manic illness is incompatible with Freudian analysis, which lasts for several years and does not work.

The question of how psychiatry and indeed many doctors were mesmerised for the best part of fifty years by the bogus
theories of Freudianism is one of the most extraordinary events of the intellectual history of the twentieth century. Its humiliation is exemplified by the case of Rafael Osheroff, as described by Edward Shorter:

In 1979, Osheroff, a 42-year-old physician from Alexandria was admitted to Chestnut Lodge Hospital with the symptoms of psychotic depression. In the course of his seven-month stay he was treated with four sessions in intensive psychotherapy a week and denied medication, despite his own requests, on the grounds that his clinicians wanted him to regress back to the point in childhood at which the initial trauma occurred and then ‘build from there'. Dr Osheroff, by contrast, merely wanted to get better and finally obtained a transfer to another private clinic where he was treated with chlorpromazine and antidepressants. Within three months he was discharged and able to return to a normal life. On returning home, Osheroff found that his world had disintegrated, his wife having left him and his partner – who had driven him to Chestnut Lodge – having ousted him from their joint practice. In 1982 Osheroff sued Chestnut Lodge for malpractice on the grounds that he should have been given state-of-the-art treatment with medication of demonstrated efficacy rather than left to vegetate for seven months. In 1987 the case was settled out of court for an undisclosed sum. Did psychoanalysis meet ‘accepted standards of care'? Gerald Clareman, an influential psychiatrist who had testified on Osheroff's behalf, made the point that the efficacy of intensive psychoanalysis had never been established. The case left a strong impression that treating major psychiatric illness with psychoanalysis alone constituted malpractice.
16

The collapse of Freudianism is now well documented. Its major fault was that beneath the veneer of rationalism (psychoanalysis as a ‘science of the mind') it was profoundly irrational, in that it located the source of mental illness in conflicts in early childhood that were inaccessible to human reason. But it was not just the drugs that killed off psychoanalysis.
17
Rather its claims to offer an explanation for the neuroses was undermined by the dramatic success of its antithesis, cognitive therapy, in the 1980s and 1990s. In contrast to psychoanalysis, cognitive therapy is simple, straightforward, lasts weeks rather than years, but above all permits the patients to make sense of, and thus control, their psychological problems. It also works – for generalised anxiety disorder, obsessive-compulsive disorder, panic disorder, agoraphobia and depression.
18

Post-war psychiatry has indeed been a ‘smashing success', but it is also deeply enigmatic. The ‘triumph' of human reason in understanding the neuroses epitomised by psychoanalysis has been shown to be a sham, while the accidental discoveries of the drugs ‘that really made a difference' were made completely independently of any intellectual understanding of mental illness.

R
EFERENCES
ABBREVIATIONS
AJM
American Journal of Medicine
AJOG
American Journal of Obstetrics and Gynaecology
BJHH
Bulletin of the Johns Hopkins Hospital
BMJ
British Medical Journal
JAMA
Journal of the American Medical Association
JRSM
Journal of the Royal Society of Medicine
MRC
Medical Research Council
NEJM
New England Journal of Medicine
OUP
Oxford University Press
PSMMC
Proceedings of the Staff Meetings of the Mayo Clinic

The place of publication is London unless otherwise stated.

Introduction

1
.
Richard Horton, ‘A Manifesto for Reading Medicine',
The Lancet
, 1997, Vol. 349, pp. 872–4.

2
.
Isobel Allen,
Doctors and Their Careers
(Policy Studies Institute, 1988); Isobel Allen,
Doctors and Their Careers: A New Generation
(Policy Studies Institute, 1994).

3
.
Anthony King,
Daily Telegraph
, 3 June 1996.

4
.
Nigel Hawkes,
The Times
, 4 February 1998.

5
.
Peter Skrabanek,
The Death of Humane Medicine and the Rise of Coercive Healthism
(Social Affairs Unit, 1994).

6
.
David Eisenberg, ‘Unconventional Medicine in the United States: Prevalence Costs and Patterns of Use',
NEJM
, 1993, Vol. 328, pp. 246–52.

7
.
Office of Health Economics,
Compendium of Health Statistics
, 1998.

A LENGTHY PROLOGUE: TWELVE DEFINITIVE MOMENTS

1
.
Lewis Thomas, ‘Biomedical Science and Human Health',
Yale Journal of Biology and Medicine
, 1978, Vol. 51, pp. 133–42.

2
.
H. H. Dale, ‘Advances in Medicinal Therapeutics',
BMJ
, 7 January 1950, pp. 1–7.

1: 1941: Penicillin

GENERAL READING

R. Hare,
The Birth of Penicillin
(Allen & Unwin, 1970).

G. Macfarlane,
Howard Florey: The Making of a Great Scientist
(Oxford: OUP, 1979).

——,
Alexander Fleming: The Man and the Myth
(Chatto & Windus,1984).

John C. Sheehan,
The Enchanted Ring
(Cambridge, MA: MIT Press,1982).

Wesley W. Spink,
Infectious Diseases: Prevention and Treatment in the Nineteenth and Twentieth Centuries
(Folkestone: Dawson, 1979).

Milton Wainwright,
Miracle Cure
(Oxford: Blackwell, 1990).

REFERENCES

1
.
Charles Fletcher, ‘First Clinical Use of Penicillin',
BMJ
, 1984, Vol. 289, pp. 1721–3.

2
.
E. P. Abraham, E. Chain, H. W. Florey
et al.
, ‘Further Observations on Penicillin',
The Lancet
, 16 August 1941, pp. 177–88.

3
.
Ronald Hare,
The Birth of Penicillin
. See also John Henderson, ‘The Yellow Brick Road to Penicillin: A Story of Serendipity',
PSMMC
, 1997, Vol. 72, pp. 683–7; Alexander Fleming, ‘Discovery of Penicillin',
British Medical Bulletin
, 1944, Vol. 2, pp. 4–5.

4
.
Alexander Fleming, ‘On the Antibacterial Action of Cultures of a Penicillium, With Special Reference to Their Use in the
Isolation of B. Influenzae',
British Journal of Experimental Pathology
, 1929, Vol. 10, pp. 226–36.

5
.
E. Chain, ‘Thirty Years of Penicillin Therapy',
Proceedings of the Royal Society of London: Series B
, 1971, Vol. 179, pp. 293–319.

6
.
E. Chain, H. W. Florey
et al.
, ‘Penicillin as a Chemotherapeutic Agent',
The Lancet
, 24 August 1940, pp. 226–8.

7
.
G. Macfarlane,
Alexander Fleming: The Man and the Myth
.

8
.
G. Macfarlane,
Howard Florey: The Making of a Great Scientist
.

9
.
H. W. Florey, ‘Penicillin',
Nobel Lectures: Physiology or Medicine, 1940–62
(New York: Elsevier, 1964).

10
.
E. F. Gale
et al.
,
The Molecular Basis of Antibiotic Action
(Chichester: John Wiley & Sons, 1981). E. F. Gale
et al.
,
The Molecular Basis of Antibiotic Action
(Chichester: John Wiley & Sons, 1981).

11
.
John C. Sheehan,
The Enchanted Ring
.

12
.
Lawrence Garrod and Francis O'Grady,
Antibiotics and Chemotherapy
(E & S Livingstone, 1971).

13
.
S. A. Waksman, ‘The Soil as a Source of Micro-organisms Antagonistic to Disease-producing Bacteria',
Journal of Bacteriology
, 1940, Vol. 40, pp. 581–600.

14
.
S. A. Waksman, ‘The Role of Antibiotics in Nature',
Perspectives in Biology and Medicine
, Spring 1961, pp. 271–87.

15
.
L. C. Vining, ‘Role of Secondary Metabolites from Microbes',
Secondary Metabolites: Their Function and Evolution
, ed. D. Chadwick and J. Whelan, Ciba Foundation Symposium 171 (Chichester: John Wiley & Sons, 1992).

2: 1949: Cortisone

GENERAL READING

E. G. L. Bywaters, ‘The History of Paediatric Rheumatology',
Arthritis and Rheumatism
, 1977, Vol. 20, pp. 145–52.

David Canton, ‘Cortisone and the Politics of Drama, 1949–55',
Medical Innovations in Historical Perspective
, ed. John V. Pickstone (Macmillan, 1992).

George D. Kersley and John Glyn,
A Concise International History of Rheumatology and Rehabilitation
(Royal Society of Medicine Press, 1992).

Albert Q. Maisel,
The Hormone Quest
(New York: Random House,1965).

Harry M. Marks, ‘Cortisone, 1949: A Year in the Political Life of a Drug',
Bulletin of the History of Medicine
, 1992, Vol. 66, pp. 419–39.

REFERENCES

1
.
Philip S. Hench
et al.
, ‘The Effect of a Hormone of the Adrenal Cortex on Rheumatoid Arthritis',
PSMMC
, 1949, Vol. 24, pp. 181–97.

2
.
Albert Maisel,
The Hormone Quest
.

3
.
Philip S. Hench, ‘Analgesia Accompanying Hepatitis and Jaundice in Cases of Chronic Arthritis',
PSMMC
, 1933, Vol. 8, pp. 430–37.

4
.
Philip S. Hench, ‘Effect of Spontaneous Jaundice on Rheumatoid Arthritis: Attempts to Reproduce the Phenomenon',
BMJ
, 1938, Vol. 2, pp. 394–8.

5
.
Philip S. Hench, ‘The Reversibility of Certain Rheumatic and Non-rheumatic Conditions by the Use of Cortisone',
Nobel Lectures: Physiology or Medicine, 1942–62
(New York: Elsevier, 1964).

BOOK: The Rise and Fall of Modern Medicine
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