The Lady Macbeth EffectIn this assignment, you will reflect on human behavior influenced by the Lady Macbeth effect. Review this simple field experiment. The study looks at the "Lady Macbeth effect."

Comment 90 www.thelancet.com Vol 369 January 13, 2007 way to reduce risks identiﬁ ed in premarketing clinical and non-clinical studies.

Despite the major advances made in ensuring transparency, important issues remain unresolved and will need further legislative initiatives.

These issues include: provision of objective and independent information to patients on medicinal products; establishment of an independent body for pharmacovigilance; and clariﬁ cation of the notion of commercially sensitive information, which companies still cannot disclose to the general public.

*G Pimpinella, R Bertini Malgarini Agenzia Italiana del Farmaco, Rome, 00144, Italy [email protected] GP was the Italian representative at the pharmaceutical group of the EU Council when the Pharmaceutical Code (Review 2001) was ﬁ nalised, during the Italian presidency of the Council. RBM participated in the review of safety aspects of legislative proposals.

1 The European Parliament and the Council of the European Union. Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use. April 30, 2004: http://ec.europa.eu/ enterprise/pharmaceuticals/review/doc/ﬁ nal_publ/dir_2004_27_ 20040430_en.pdf (accessed on Sept 29, 2006).

2 The European Parliament and the Council of the European Union.

Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency.

April 30, 2004: http://ec.europa.eu/enterprise/pharmaceuticals/review/ doc/ﬁ nal_publ/reg_2004_726_20040430_en.pdf. (accessed on Sept 29, 2006).

3 Garattini S. Conﬁ dentiality. Lancet 2003; 362: 1078–79.

4 European Medicines Agency. Index of centrally authorised medicinal products. http://www.emea.europa.eu/htms/human/epar/a-zepar.htm# (accessed Oct 17, 2006).

5 Abraham J, Lewis G. Secrecy and transparency of medicines licensing in the EU. Lancet 1998; 352: 480–82.

6 Judgment of the Court of First Instance (Fifth Chamber) on 18 December 2003 in Case T-326/99. http://curia.europa.eu/jurisp/cgi-bin/ form.pl?lang=en&Submit=Submit&alldocs=alldocs&docj= docj&docop=docop&docor=docor&docjo=docjo&numaﬀ =T-326%2F99 &datefs=&datefe=&nomusuel=&domaine=&mots=&resmax=100 (accessed Oct 17, 2006).

7 Horton R. Vioxx, the implosion of Merck, and aftershocks at the FDA.

Lancet 2004; 364: 1995–96.

8 Maxwell SR, Webb DJ. COX-2 selective inhibitors: important lessons learned. Lancet 2005; 365: 449–51.

9 European Medicines Agency. ICH topic E 2 E: pharmacovigilance planning (Pvp)—step 5, note for guidance on planning pharmacovigilance activities (CPMP/ICH/5716/03). June, 2005: http://www.emea.eu.int/pdfs/ human/ich/571603en.pdf (accessed Sept 13, 2006).

Quite reasonably emotional The Macbeth eﬀ ect, a term recently minted by Chen-Bo Zhong and Katie Liljenquist, management researchers from Canada, summarises the ﬁ ndings of a set of slightly offb eat experiments exploring the relation between people’s physical and moral purity. 1 In one task, individuals who had ﬁ rst been asked to describe an unethical deed from their past then had to complete several words by ﬁ lling in the missing letters. The words they created were more likely to be linked to cleansing (eg s--p completed as soap rather than step, or w--h as wash rather than wish) than those completed by others who had been asked to recall an ethical act. In a related test, participants were oﬀ ered a choice of small gifts: a pencil or an antiseptic wipe. Those who had recalled unethical actions were twice as likely to take the wipe.

Even more striking were the results of a further experiment that showed how cleaning the hands immediately after giving an account of an unethical deed reduced the likelihood of volunteering, unpaid, to help an impoverished graduate student with his experiments.

Having washed their hands, so we are told by Zhong and Liljenquist, participants had subconsciously erased their moral stains and so felt less need to compensate by behaving altruistically. All in all, say the researchers, the ﬁ ndings “shed light on Lady Macbeth’s feverish attempts to physically cleanse herself following the murder of King Duncan”.

Compressed into a couple of paragraphs, work of this kind is apt to seem naive if not downright risible. This conclusion is unfair. What such research represents is the latest faltering steps of an enterprise still in its infancy:

the biology of ethical and moral reasoning. Among the pioneers of this endeavour are workers at Princeton University’s Center for the Study of Brain, Mind and Behavior. Set up by psychologist Jonathan Cohen in 1998, the centre aims to tease out the processes underlying, among other things, moral behaviour. A study by Joshua Greene, until recently a postdoctoral fellow at the centre, neatly illustrates the intention.

Greene joined Princeton with a philosophy degree and the urge to bring a more empirical approach to his discipline. His topic was the role of emotion versus reason in making moral judgments; 2 his main investigative method was the increasingly ubiquitous functional MRI.

In his main experiment, he asked participants how they would respond in two situations. In the ﬁ rst, they are Comment www.thelancet.com Vol 369 January 13, 2007 91 watching ﬁ ve people in a trolley rolling down a railway track towards a cliﬀ edge. They can save the ﬁ ve by throwing the lever of a set of points to divert the trolley— but doing so will kill a person standing on this second track. Although one life will be sacriﬁ ced, ﬁ ve will be saved, and most people say they would throw the lever. In the second scenario, the individuals imagine themselves standing next to an exceptionally fat man on a footbridge over the track. This time they can stop the runaway trolley by pushing their companion on to the track in front of it.

Here too, one man will die, but ﬁ ve will be saved. In this case, however, most people say they would not take action.

Philosophers have yet to devise a watertight reasoned justiﬁ cation for the diﬀ ering decisions. So Greene decided to look for another kind of explanation—and he found it. By putting the two situations to his participants while they underwent functional MRI, he was able to show that contemplating the footbridge dilemma prompted more activity in areas of the brain associated with emotion than did the points scenario.

Greene’s ﬁ ndings challenge the view that moral judgments must be based entirely on reason. Indeed, he believes that emotion is a legitimate and inescapable part of moral decision-making. Other ﬁ ndings support this idea. Moll and colleagues, 3 working in the USA and Brazil, studied brain activation in individuals shown various disturbing images. Some of these (war scenes, physical assault) had a clear moral content; others (body lesions, dangerous animals) did not. Functional MRI scans showed that the images’ moral content, or lack of it, inﬂ uenced the precise distribution of brain activity—but with substantial overlap between the two categories. In short, moral and emotional responses were distinguishable, but not wholly separable.

As Greene points out, such work is not intended to discern right from wrong. But, in a host of ethical issues from abortion to euthanasia, a better understanding of the mechanisms underpinning our moral judgments could alter our attitude to them. Whether such decisions would, as a consequence, become easier to make or harder remains an open question.

During the past few decades, we have witnessed the ethical analysis of science and medicine becoming a growth industry, generating jobs, journals, university departments, and tidal waves of sometimes tendentious punditry. By contrast, the attempt to put the relation into reverse—to oﬀ er a scientiﬁ c analysis of the nature and process of decision-making in ethics—has barely begun.

That we should now be doing so seems entirely ﬁ tting.

Geoﬀ Watts 28 New End Square, London NW3 1LS, UK geoﬀ @scileg.freeserve.co.uk I declare that I have no conﬂ ict of interest.

1 Zhong CB, Liljenquist K. Washing away your sins: threatened morality and physical cleansing. Science 2006; 313: 1451–52.

2 Greene JD, Sommerville RB, Nystrom LE, Darley JM, Cohen JD. An fMRI investigation of emotional engagement in moral judgment. Science 2001; 293: 2105–08.

3 Moll J, de Oliveira-Souza R, Eslinger PJ, et al. The neural correlates of moral sensitivity: a functional magnetic resonance imaging investigation of basic and moral emotions. J Neurosci 2002; 22: 2730–36. Lady Macbeth Paper of the year 2006 2006 was a busy year for biomedical researchers, with over 700 000 papers indexed on PubMed. So deciding which of those papers is deﬁ nitively the best is an impossible task, as even the most dedicated of judges would struggle to read a tiny percentage of them. But for the past 3 years The Lancet’s editors have singled out a Paper of the Year. The rules this year were simple: the paper had to have a publication date in 2006 and the Getty Images The printed journal includes an image merely for illustration