How to make beasts nervy

International Journal of Neuropsychopharmacology
May 12, 2000

My school class was once given the poem "To a Mouse" by Robert Burns to learn, with the prospect of having to recite. Fifty-four years on, I can still hear those lines: "Wee, sleekit, cow'rin, tim'rous beastie /O what a panic's in thy breastie!" But I was astounded to see them quoted in a paper in this new journal titled "Knockout corner: 5HT1A receptor inactivation: anxiety or depression as a murine experience". By genetic jiggery-pokery, mice have been created that lack a particular receptor for serotonin (a chemical agent transmitting nerve signals in the brain). These mice seem to display behavioural patterns indicating that they are more anxious, that is they have more panic in their breasties. Thus is the poetry of Burns distilled to the artifices of neuroscience.

The archaically named Collegium Internationale Neuropsychopharmacologicum (CINP) established The International Journal of Neuropsychopharmacology ( IJNP ) in 1998. CINP is a society composed of non-clinical and clinical scientists, the latter usually psychiatrists of many nationalities who are interested in the workings of the brain in relation to the mind and its disorders, the nature and function of the chemical signalling agents in the nervous tissue of the brain, and the effects of drugs on all that. The subject implicitly encompasses all disorders of the mind, from anxiety through manic depressive disease and schizophrenia to the ravages of Alzheimer's disease.

The editor-in-chief, Bernard Lerer, is a greatly respected neuro-psychopharmacologist working in Jerusalem. The brief that he and his field editors have set themselves is an exciting one.

The advances in basic neuroscience, particularly in neurobiology, are amazing and show no sign of decreasing. On the back of them, the applied science of neuro-psychopharmacology will bloom. Remember, you basic scientists, that you may discover a molecular interaction in the brain (and in our present state of ignorance that should not be difficult), but if it is to be of clinical relevance, someone has to cross the great divide from basic science to the patient. Human experimentation has to be done safely and ethically by well-trained clinicians, usually biological psychiatrists, with all the difficulties that experimenting on people involves.

Having made discoveries at the basic and clinical levels, and spanning both for most of my career, I have no doubt that working at the basic level is much easier than at the clinical. Drugs are aimed at molecular targets. To go from there to the whole patient requires a leap of faith over a minefield of uncertainties that many basic neuroscientists neither respect nor fully understand. The ethical issues are considerable. One cannot easily justify using a placebo in a clinical trial of antidepressant drugs when effective treatments already exist. The question has to become: "Is this new drug better than existing treatment? " That is a more difficult question to answer, which requires the study of many more patients and adds considerably to the cost.

From its inception, IJNP has published research articles on functional psychopharmacology ranging from the basic science to its clinical application. It has sections for lengthy research articles, for brief research reports, for reviews of basic and clinical science and for helpful shortish articles on trends and perspectives. Burns's mouse appeared in the last.

What the world can do without, however, is the publication of abstracts of posters and short communications at meetings in a society's journal. It fools no one in the citation stakes, those vainglorious ciphers beloved of bureaucratic academic accountants. We, the academic community, should stop it and rely solely on computer technology for the communication of abstracts.

From the editorial in the first volume comes the statement:

"Neuro-psychopharmacology is still a very young discipline. This manifestsI in ferment, rapid shifts in priorities and fluidity of fundamental concepts. The critical observer cannot but concede that the tenets of contemporary neuro-psychopharmacology could turn outI to be incorrectI These attributes are what gives neuro-psychopharmacology its allure."

I agree with the essentials of this statement, but while these properties of a science appeal to some, they are not for everyone. Some people find rapid shifts in priorities and fluidity of fundamental concepts in a science unalluring. Neuro-psychopharmacologists should ask themselves whether fickleness, which they extol as a virtue, is but a manifestation of the quickness of the footwork or the sleight of the hand of the neuro-psychopharmacologist, who is moving on before he is found out.

Sometimes I have had that feeling, and I have to admit that I, too, behaved in that way and have been criticised for it. My honest excuse is that if the boat is not moving on its current tack then try another, particularly if one is in unknown waters; and in psychopharmacology one usually is. If you are committed to a particular field, you have to cope with its personality, which may be different from that of another related field, which can in turn require different investigative behaviour.

In my experience, much of neuro-psychopharmacology is not like "straight" science with clear objectives, identified pathways of investigation, available technology and predictable, or at least deducible, outcomes. Until the basic neurobiological background of the subject is better understood, rapid shifts in priorities and fluidity of concepts will remain. Do not let us feel embarrassed by that, let us just get on with the job and try to explain to the scientific world what we are doing. That is what this journal is for.

But watch out, neuro-psychopharmacologists. The genomics boys are coming and the "wee tim'rous beastie" is likely to be taken up by a new discipline: molecular (to emphasise focus and reductionism), genomic (to emphasise important and fashionable science), neuro-psychopharmacology (thus implying that this old-new science is going to be sorted out by two new adjectives). Want to start a new journal?

David Grahame-Smith is professor of clinical pharmacology, University of Oxford.

International Journal of Neuropsychopharmacology: Four times a year

Editor - Bernard Lerer
ISBN - ISSN 1461 1457
Publisher - Cambridge University Press
Price - £112.00 (institutions); £56.00 (individuals)
Pages - -

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