Table Of ContentThe
Psychopharmacologists
Interviews by Dr David Healy
A member of the Hodder Headline Group
LONDON· NEW YORK· NEW DELHI
First published in Great Britain in 1996 by Chapman & Hall.
This impression published by
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Contents
Contributors vu
Preface 1X
Acknowledgements XVll
Glossary
X1X
Dramatis personae
XXV
Chronology of interviews XXXlll
1 Pierre Pichot (Paris) 1
The discovery of chlorpromazine and the place of
psychopharmacology in the history of psychiatry
2 ]ulius Axelrod (NIMH) 29
The discovery of amine reuptake
3 Arvid Carlsson (Gothenburg) 51
The rise of Neuropsychopharmacology:
impact on basic and clinical neuroscience
4 Frank Ayd (Baltimore) 81
The discovery of antidepressants
5 Alan Broadhurst (Cambridge) 111
Before and after imipramine
6 Silvio Garattini (Milan) 135
The role of independent science in psychopharmacology
7 Heinz Lehmann (Montreal) 159
Psychopharmacotherapy
8 Hanns Hippius (Munich) 187
The founding of the CINP and the discovery of clozapine
9 Hannah Steinberg (London) 215
Bridging the gap: psychology, pharmacology and after
10 ]onathan Cole (Harvard) 239
The evaluation of psychotropic drugs
11 Alex Coppen (Epsom) 265
Biological psychiatry in Britain
12 ]ules Angst (Zurich) 287
The myths of psychopharmacology
VI The Psychopharmacologists
13 George Beaumont (Cheshire) 309
The place of clomipramine in psychopharmacology
14 Donald Klein (New York) 329
Reaction patterns to psychotropic drugs and the discovery
of panic disorder
15 Herman van Praag (Maastricht) 353
Psychiatry and the march of folly
16 Merton Sandler (London) 381
The place of chemical pathology in psychopharmacology
17 Floyd Bloom (Scripps) 401
Neurophysiology and the psychopharmacology of the addictions
18 Alexandra Delini-Stula (Basle) 425
The changing face of psychotropic drug development - from
1965 to 1995.
19 Gordon Claridge (Oxford) 441
The role of individual differences in psychopharmacology
20 Malcolm Lader (London) 463
Psychopharmacology: clinical and social
21 Herbert Meltzer (Ohio) 483
A career in biological psychiatry
22 Brian Leonard (Galway) 509
The role of behavioural pharmacology in drug development
23 John Hughes (Cambridge) 539
The discovery of the opioid peptides
24 Peter Waldmeier (Basle) 565
From mental illness to neurodegeneration
25 Tom Ban (Toronto) 587
They used to call it psychiatry
Index 621
Contributors
]ules Augst
Department of Psychiatry, Psychiatrische Universiteats Klinik Zurich,
Postfach 68, CH-8029, Zurich 8, Switzerland.
Julius Axelrod
Laboratory of Cell Biology, National Institute of Mental Health, Building
36, 9000 Rockville Pyke, Bethesda, Maryland 20892, USA
Frank Ayd
1130 East Cold Spring Lane, Baltimore, Maryland 21239-3931, USA
Thomas A. Ban
1177 Yonge Street, Toronto, Ontario M4T 2Y4 , Canada
George Beaumont
11 Dorchester Road, Hazel Grove, Stockport, Cheshire SK7 SHE, UK
Floyd Bloom
Department of Neuropharmacology, The Scripps Research Institute,
10666 North Terney Pines Road, La Hella, California 92037, USA
Alan Broadhurst
Vicarage Grove, The Park, Great Barton, near Bury St Edmonds, Suffolk
IP31 2SU, UK
Arvid Carlsson
Department of Pharmacology, University of Gothenburg, Mediconarega
tan 7, S-41390 Gothenburg, Sweden
Gordon Claridge
Magdalen College, Oxford OX1 4AU, UK
Jonathan Cote
57 Ellery Street, Cambridge, Massachusetts 02138, USA
Alec Coppen
5 Walnut Close, Downs Road, Epsom, Surrey, UK
viii The Psychopharmacologists
Alex Delini-Stula
Roche International Clinical Research Center, Pare Club des Tanneries,
BP 83, F-673 82 Lingoisheim, France
Silvio Garattini
Director, Institue de Ricerche Farmacologiche 'Mario Negri', Via Eritrea
62, 20157 Milan, Italy
Hanns Hippius
Am Forst 4-A, 82166 Grafelfing, Germany
John Hughes
Director, Park-Davies Neuroscience Centre, Addenbrooke's Hospital, Hill
Road, Cambridge CB2 2QB, UK
Donald R Klein
1016 Fifth Avenue, New York NY 10028, USA
Malcolm Lader
Institute of Psychiatry, Clinical Psychopharmacology Section, De Cres
pigny Park, Denmark Hill, London SE5 8AF, UK
Heinz Lehmann
1212 Pine Avenue, Montreal, Quebec H39 1A9, Canada
Brian Leonard
Department of Pharmacology, University College, Galway, Republic of
Ireland
Herbert Meltzer
Department of Psychiatry, Hanna Pavilion, 2040 Abingden Road, Cleve
land, Ohio 44104, USA
Pierre Pichot
24 rue de Fosses, Saint Jacques 75005 Paris, France
Merton Sandler
Department of Chemical Pathology, Queen Charlotte's Maternity Hospi
tal, Goldhawk Road, London W6 OXG, UK
Hannah Steinberg
Health Research Centre, School of Psychiatry, Middlesex University,
Queensway, Enfield EN3 4SF, UK
Herman van Praag
Professor and Chairman, Academic Psychiatric Centre, University ofLim
burg, PO Box 616, 6200 MD Maastricht, The Netherlands
Peter Waldmeier
K-125,607, Ciba-Geigy Limited, Basle, Switzerland
Preface
The impetus to put this book together came from a number of sources.
One was a need to do some research for a history of the period (see
References). During the course of this, it became clear that others might
also be interested in the raw material of the interviews and might have
quite differing interpretations. The precipitating event was a train ride
with George Beaumont from London to Guildford. This only takes an
hour or so; just as the train pulled out, for whatever reason, I told George
I'd been thinking about doing this and his story about how he targeted
clomipramine for OCD was one of the ones I'd be interested to have.
We looked at each other, I whipped out a tape recorder and we began
the first interview. There are a number of interviews in the book that are
almost verbatim as they were first recorded. George's is one of these.
Another was Silvio Garattini's, which was done in the dark in the back
of a taxi while travelling from Heathrow into London. Once a few had
been done, the project just grew.
There were a few things I was keen to chase, which didn't come out.
One of these was an idea that science operates more often because of
clashes of personality than anyone suspects. A good example involved the
race for absolute zero, which happened between groups in England and
Holland at the turn of the century. The English lost out because the two
people who needed to cooperate with each other in order to produce a
result, Ramsay and Dewar, weren't prepared to talk to each other. The
psychoanalytic story, similarly, is a story of people coming to particular
viewpoints almost to spite someone else rather than because of the intrinsic
merits of their position. Now this may have to do with ambition and
priority issues but you also have to check and see that things are not
happening because of who stole whose wife, for instance. Indeed one of
the wives put it to me that I might find out more about the history
of psychopharmacology by interviewing the wives rather than the 'great
men' themselves. There's something to be said for this. You can often
gauge the real reaction to a person or an event from a spouse where the
participant in the event has to inhibit their feelings because the game is
ongomg.
Part of the reason this kind of material didn't actually emerge may have
x The Psychopharmacologists
been that the people I've interviewed came out on top, so they have less
need to recall these things. There was a reluctance or at least a caution
about speaking ill of others. Nevertheless there are clashes buried in the
interviews that can be traced by looking at who fails to cite whom, even
when they worked in the same institution. And there have been very
visible clashes, as in the discovery of the opioid peptides, recounted by
John Hughes, and the story of the evaluation of lithium, which got fairly
personalized. There have also been clashes around the foundation of
ECNP, BAP and CINP, which seem to have involved the clash of person
ality styles.
Personality styles - or historical forces as expressed through personal
ities? Another motive to do these interviews was that at the time I was
the Secretary for the British Association for Psychopharmacology and I
thought it would be a good idea to chase the origins of the BAP. Now
at just this time, the Presidency of the BAP had become a hot political
issue. For 20 years the question of who was going to be the next President
had been a fix but in 1994, it was bitterly contested, with all sorts of
personalized comments flying around and skullduggery that came close
to being actionable.
On one level, the issues were pitched as a battle between the fixers,
who wanted to stitch things up behind the scenes, and those who wanted
a transparent democracy. To my surprise, I found myself on the fixer side
of the argument. This I think was because these things never come as
single issues. Open democracy as I saw it was being linked to a particular
view of how science operates, the classical idea that we should be system
atically testing models, as opposed to a pragmatic 'let's fish' model. On
this level the fishing model is much more open and democratic while the
purist model can be something of a stitch-up - at least as I saw it then.
Historically, psychopharmacology has been a pragmatic exercise, whereas
neuroscience, which is springing forth, Athena-like from it, is classically
principled. Add in the personality end of it and you have the historical
dilemma of trying to decide how much of history is down to personalities
- would we have had the Second World War without Hitler; would the
Northern Ireland problem have been as bad without Paisley? Given that
I was arguing for a position that in many respects was alien to me, I was
left wondering how much we become the pawns of historical forces,
which produce a situation in which people who would otherwise have a
lot in common end up divided by deep animosities.
I took these issues with me into many of the interviews - where
are societies like the British Association and the American College for
Neuropsychopharmacology situated today? What's going to happen them?
The ACNP has thrown off a Society for Clinical Psychopharmacology
and it's not clear how the BAP will evolve. In some ways, societies like
the ACNP and BAP can act as the miner's canary for changes in the
scientific atmosphere because they are relatively pure scientific societies,
Preface XI
rather than semi-trade unions like the American Psychiatric Association or
the Royal College ofPsychiatrists. ACNP/BAP are shaped by completely
different dynamics to the APA/RCP. Committee behaviour anywhere in
my experience involves illusory intimacies between people who when the
going gets difficult are usually more concerned to ensure that no one
shouts too loud in case the neighbours are listening than they are about
anything else. But because the preserve of professional turf is not on the
agenda for BAP, in practice what happens is much less likely to be
dictated by the actions of people who may be almost openly referred to
as blustering bullies but whose behaviour cannot be or is not contained.
Another reason for trying to put a history together can be to try to
make sense of what has happened in one's own life. Having trained in
medicine, I got involved in psychopharmacology research, partly for the
not-very-elevated reason that it seemed a good idea in order to be able
to get some control over the kind ofj obs I might want. The only research
happening in Ireland in 1980 that seemed in any way relevant was with
Brian Leonard- looking at what psychotropic drugs did to 5-HT reup
take. At the time, it seemed that working on these drugs was one of the
few serious ways into the brain and the mind and the inter-relationships
between brain and behaviour.
In my case, however, this led away from the now highly topical area of
amine reuptake to work on circadian rhythms in affective disorders. I
happen to think that a circadian model is much more persuasive than the
amine theories ever were. There are coherent competing hypotheses to
choose between - so it should be of interest to the purists but on the
contrary the whole area has remained a backwater. The other area I've
been involved in has been giving drugs to healthy human volunteers to
test what effects these have on mental functioning with a view to working
backwards from that to how the brain works - but the whole area is
closing down it seems. It's difficult to get ethical committees or funding
agencies to agree to projects even though the agents in question may have
little more effect than, say, coffee. This seems to represent an important
'loss of nerve' and trying to trace the origins of this has been another
reason to examine the history. To paraphrase Oscar Wilde, if one area of
research you're involved in gets eclipsed, that's bad luck but if two do,
you have to wonder what's going on.
Fairly early in my 5-HT uptake career, it seemed to me that far from
being descriptions of any reality, the amine theories were simply a case of
the politically correct language - the language that had triumphed because
you've got to have some view about what the drugs are doing. The
psychodynamic theories were at a major disadvantage even though they
were much more complex and subtle theories because they couldn't
account for one of the obvious features of modern practice, which is that
psychotropic drugs work. Even simplistic biological theories were better
placed from that point of view. There have been tremendous advances
