History and humanities

Responding to Crisis Malaria in the Australian Defence Force during and after participation in the International Force in East Timor (INTERFET) Scott J Kitchener, Alyson M Auliff and Karl H Rieckmann Malaria in Australian Defence Force members has been far more common in East Timor than in other recent overseas deployments. By six months after all 5500 members of the International Force in East Timor had returned to Australia, 267 malaria infections had been reported to the Army Malaria Institute. Only 64 of those affected had their first clinical episode during their 4-5 months in East Timor, and about two-thirds of these infections were caused by Plasmodium falciparum. The remaining 212 soldiers developed their first symptoms after returning to Australia, and all but two infections were caused by P. vivax. After treatment, 44 soldiers had relapses of their vivax infections; 11 had a second relapse and two had a third relapse. These findings raise several issues about prevention and management of malaria in the ADF. MJA 2000; 173: 583-585 Antimalarial measures - High malaria rates in two battalions - Notification of malaria infections - Malaria infections with onset in East Timor - Malaria infections with onset in Australia - Parasite resistance to drugs? - References - Authors' details - - More articles on Infectious diseases and parasitology On 12 September 1999, President Habibie of Indonesia invited an international peace-keeping force to help restore peace in East Timor after significant civil unrest. The United Nations Security Council Recommendation 1264 (15 September 1999) directed the formation of an International Force in East Timor (INTERFET). On 20 September, lead elements of INTERFET from the Australian Defence Force (ADF) landed in Dili and were soon followed by approximately 5500 ADF personnel assigned to serve in different parts of East Timor. INTERFET concluded on 23 February 2000, when most ADF personnel came under the command of the Peace Keeping Force of the United Nations Transition Administration for East Timor (UNTAET). Antimalarial measures ADF personnel used various personal protection measures against mosquitoes, including insect repellents and permethrin-treated mosquito-nets. Preventive medicine units also carried out mosquito control measures. Personnel were given doxycycline (100 mg daily) for prophylaxis, starting one or two days before departure for East Timor and continuing for two weeks after return to Australia. Weekly doses of mefloquine (250 mg) were used as an alternative if doxycycline prophylaxis was not tolerated or contraindicated. In addition, terminal prophylaxis with primaquine (7.5 mg three times daily) was given for two weeks after return to Australia. In general, chemoprophylaxis was not taken under supervision. High malaria rates in two battalions On 23 October 1999 -- approximately one month after deployment -- the first malaria infection was diagnosed in a soldier serving with the Second Battalion, Royal Australian Regiment (2RAR). During the four months of the battalion's deployment on the northern border region, mainly during the wet season, 17 members of the battalion developed malaria (monthly rate, 0.71%). Most of these cases were traced to exposures in Batugade (see Box 1). The Third Battalion (3RAR), deployed to the Oecussi (Ambino) enclave for five months, reported 24 cases of malaria (monthly rate, 0.73%). These malaria attack rates were the highest observed during the ADF involvement in INTERFET. Based on data from ADF units deployed to other areas of East Timor, other high risk areas were the mouth of the Komoro River in Dili (near the international airport) and the southern border regions near Suai. Within 7-8 months after returning to Australia, a further 127 soldiers from 2RAR and 3RAR had developed malaria. Combined with the 41 cases with onset overseas, this equates to nearly three (2.96) of every 100 soldiers from these two battalions acquiring malaria for every month's deployment to East Timor. This rate is higher than that experienced by Australian military forces deployed recently to Southeast Asia and Africa1 and Bougainville (unpublished), but lower than that observed during some military deployments to Papua New Guinea.2 Notification of malaria infections That malaria was a health problem was obvious during the five-month duration of INTERFET, and this became even more noticeable after the return of troops to Australia. Clinical episodes of malaria were reported to the Central Malaria Register of the ADF, which is managed by the Army Malaria Institute (AMI). The AMI records clinical and epidemiological data, and, whenever possible, confirms the diagnosis by microscopic examination of blood films or polymerase chain reaction (PCR). Malaria infections with onset in East Timor During deployment of the entire Australian contribution to INTERFET, 64 ADF members developed malaria while in East Timor (Box 2a). About two-thirds of these infections were caused by Plasmodium falciparum and the remainder by P. vivax. This 2:1 ratio reflects the relative prevalence of these two species in the local communities,3 and suggests that there was inadequate compliance with doxycycline prophylaxis or that there were other factors resulting in lower drug concentrations, such as drug deterioration under adverse environmental conditions or reduced bioavailability. The falciparum infections were treated with either a one-day course of mefloquine, or quinine (3 days) combined with doxycycline (10 days). One patient tolerated mefloquine poorly and received atovaquone and proguanil (3 days). None of the patients had a recurrence of clinical symptoms and were presumably cured of their infections. The vivax infections were treated with a combination of chloroquine (3 days) and primaquine (14 days). All affected patients responded well to treatment, but a few had a recurrence of clinical symptoms and parasitaemia (relapse) a few weeks to months later (Box 2b). Malaria infections with onset in Australia Many more malaria infections had their onset after soldiers had left East Timor, with the first clinical episode of malaria occurring in 212 ADF members after their return to Australia (Box 2a). They all had vivax malaria, except for two soldiers who developed falciparum malaria within two weeks of their return. This indicates that doxycycline prophylaxis effectively prevented the development of the blood stages of P. vivax, but that dormant parasites (hypnozoites) in the liver reactivated, entered the bloodstream, and initiated acute attacks of malaria after doxycycline prophylaxis was discontinued. Such initial episodes of vivax malaria could occur many months after return to Australia, with most ADF personnel involved in INTERFET leaving East Timor between December and March 2000 (Box 2b). A few more initial infections will undoubtedly emerge up to 12 months or longer after return from East Timor. It was obvious that terminal prophylaxis with primaquine had not been successful in eradicating all the residual hepatic parasites. As primaquine is the only drug capable of eliminating such parasites, the 210 patients hospitalised with vivax malaria received primaquine again (22.5 mg or 30 mg daily) in addition to a standard course of chloroquine (3 days). Compliance with treatment courses was undoubtedly better than with terminal prophylaxis. Forty-four soldiers had relapses 22-180 days (median, 77 days) after treatment. Although most soldiers were cured after a second course of chloroquine and primaquine, 11 had a second relapse 28 to 157 days (median, 82 days) after treatment and two had a third relapse 145 to 159 days after the third course of treatment. Apart from the distress caused by these recurrent acute episodes of malaria, the overall effect on operational capability was quite substantial. Clearly, there is an urgent need for more effective malaria prophylaxis. Parasite resistance to drugs? Doxycycline has proven to be very effective in the past for prophylaxis of both falciparum and vivax malaria. In combination with any rapid-acting drug, it also cures falciparum infections provided it is taken for 7-10 days. All the falciparum infections in East Timor were cured after treatment with doxycycline, indicating that the parasites had not developed resistance to doxycycline. Primaquine tolerance is a well-recognised phenomenon in Papua New Guinea2 and other Melanesian countries, but it has not been well documented in East Timor. The surprisingly large number of soldiers who developed vivax malaria after returning to Australia obviously had their infections suppressed effectively by doxycycline while they were in East Timor. Their delayed malaria attacks after their return were the result of either deteriorating drug compliance or primaquine-tolerant hepatic parasites. The fact that 44 (21%) of the 210 patients with vivax malaria had a relapse of their infections (a quarter on more than one occasion), under more closely supervised drug administration, indicates that primaquine-tolerant parasites are present in East Timor. Efforts currently being made to reduce the many malaria casualties in East Timor are summarised in Box 3. References Shanks GD, Roessler P, Edstein MD, Rieckmann KH. Doxycycline for malaria prophylaxis in Australian soldiers deployed to United Nations Missions in Somalia and Cambodia. Milit Med 1995; 160: 443-445. Rieckmann KH, Yeo AET, Davis DR, et al. Recent military experience with malaria chemoprophylaxis. Med J Aust 1993; 158: 446-449. World Health Organization. East Timor epidemiological profile, September 1999 <http://www.who.ch/eha/> (accessed November 2000). Authors' details Army Malaria Institute, Gallipoli Barracks, QLD. Scott J Kitchener, FAFPHM FACTM, Officer Commanding Clinical Field Section; Alyson M Auliff, BSc(Hons), Scientific Officer, Clinical Field Section; Karl H Rieckmann, MD, Director. Reprints: Major S Kitchener, AMI, Gallipoli Barracks, Milpo, QLD 4152. scott.kitchenerATdefence.gov.au Make a comment 1: East TimorMap showing Batugade and the Oecussi (Ambino) enclave, identified as sources of infection for the Secound and Third Battalions, Royal Australian Regiment. Back to text 2: Pattern of malaria infections during the deployment of the International Force in East Timor (INTERFET) (a) Distribution of malaria type and place of onset for the 267 infections among INTERFET peronnel deployed from September 1999 to March 2000. (Data collected up to September 2000). (b) Time of onset of 210 initial vivax malaria infections and 57 relapses after return to Australia (between December 1999 and March 2000). Back to text 3: Improvement of malaria control measures Increased vigilance for malaria in the border areas of East Timor, and continued surveillance of malaria infections after redeployment to Australia; Assessment of the effectiveness of personal protection measures and remedial measures to improve compliance; Evaluation of higher doses of primaquine for eradicating parasites from the liver; and Appraisal of the effectiveness of alternative control measures, including new prophylactic drug regimens. Back to text Plasmodium falciparum Plasmodium vivax

Scott J Kitchener · Alyson M Auliff · Karl H Rieckmann

Responding to Crisis Medical assistance to civilians during peacekeeping operations: wielding the double-edged sword Michael C Reade Peacekeeping operations have become the main operational activity of the armed forces of the developed world over the past 10 years -- a trend which appears likely to continue. Peacekeepers often remain deployed long after the armed conflict has ceased to help reconstruct civilian infrastructure. It is often possible to use the excess capacity of medical support units deployed with military forces to provide help to the local population. While this is appropriate immediately after a conflict when civilian clinics are overwhelmed, in the more prolonged reconstruction phase the seemingly simple clinical imperative to treat as many patients as possible becomes more complex. MJA 2000; 173: 586-589 The civilian situation - Treating civilians at the military hospital - Potential benefits of a foreign military medical presence - Potential benefits to the military hospital in aiding the civilian population - Potential disadvantages of a foreign military medical presence - Obstacles in aiding the civilian population - Conclusions - Acknowledgements - References - Authors' details - - More articles on Military medicine The difficulties of knowing how best to help a civilian population during rebuilding after armed conflict are illustrated by the experiences of a North Atlantic Treaty Organization (NATO) Stabilisation Force (SFOR) Multinational Integrated Medical Unit. Our hospital, which was accommodated in a disused factory complex in Sipovo in the Republica Srpska of Bosnia-Herzegovina, had one operating theatre, a four-bed intensive care unit, and a 12-bed general ward. There were two anaesthetists, one general surgeon, one orthopaedic surgeon, one physician and three general duties medical officers. Our primary role to was provide immediate care to 8000 NATO personnel. Front entrance of the destroyed factory which housed our hospital The civilian situation The Sipovo area has a civilian population of around 15 000. The 3000 Muslims living in the area were "ethnically cleansed" by Serb forces at the start of the 1992-1995 war, and, despite the best efforts of the international community, few have since returned. At the end of the war, Croat forces destroyed 65% of the buildings before their departure.1 The medical clinic had been completely destroyed. Rebuilt largely with overseas aid, the clinic is now run by nine Bosnian Serb general practitioners. There are no inpatient facilities. Management decisions are often guided by availability of consumables rather than best medical practice. Were it not for our military hospital, patients requiring a higher level of care would be driven for two hours in a private vehicle or one of the two "ambulances" (minibuses with red crosses) to the civilian hospital in the nearest large city, Banja Luka. There is no civilian aeromedical retrieval facility. Banja Luka hospital was a modern tertiary referral centre before the war, but is now chronically starved of funds. Treating civilians at the military hospital In light of the generally poor civilian health services in Bosnia, it may seem incongruous that we attempted to restrict the use of our hospital by local civilians. When the hospital opened in 1996,2 the first NATO unit to deploy undertook substantial humanitarian programs, including helping to establish local primary care clinics and to reconstruct the general urban infrastructure. The emphasis was on assisting a return to self-sufficiency; there was a fear of creating dependency on NATO. "Life and limb" surgery on civilians was undertaken, but elective surgery was not permitted. The policy at that time was that no facility could be provided which did not exist before the conflict. There had never been a surgical hospital in Sipovo. Destroyed apartment complex, Sarajevo By 2000, the guidelines had been relaxed. All patients were to be first assessed at the civilian clinic, but could be referred to our hospital if management -- emergency or elective -- was beyond their resources. Any minor emergency cases were to be sent back to the clinic, though what constituted "minor" was left to the discretion of the SFOR doctor. In practice, even our more relaxed guidelines proved difficult to enforce. Patients would arrive at our gate with an illegible referral note (usually written in Latin), or with no note at all. Our young, non-medical sentries saw only a patient in distress, and would understandably want to help. By the time the diagnosis had been established, it was difficult to turn away patients who had been inappropriately referred. We saw 10-15 civilian emergency presentations a week, mainly after hours. Many did not fall within our strict criteria, but few were turned away. In addition to this emergency service, civilians formed the bulk of the work of our specialty clinics. We accommodated up to three new referrals each day, plus patients returning for follow-up. We performed elective surgery, but could accept no more than three civilian patients at one time, and accepted no elective case where the postoperative hospitalisation was expected to exceed four days. During the first six months of 2000, 66 of the 137 operations performed in our theatre were on civilians; 37 (56%) of these were elective cases (mainly hernia repairs, cholecystectomies, and minor plastic surgery). The extent of the elective services we provided was officially left to the judgement of the individual clinicians. Should we have used our "spare" capacity in this way? Should we have actively encouraged even greater use? Potential benefits of a foreign military medical presence Patients can be treated locally at a standard comparable with First World medical practice -- The standard of care we offered was probably better than that provided in the overstretched Banja Luka hospital two hours away. Once a civilian patient had been admitted to our hospital, there was no restriction on resources. Unlike in the civilian hospital, there was no cost to the patient or the Bosnian government, and it could be argued that this should free resources for use in other reconstruction projects. Local doctors can receive training and military surgeons can perform operations which have been beyond the capacity of local surgeons -- This applies more in less developed countries. As medical services in Yugoslavia had been relatively advanced, there was little need for this type of work. The problem was more lack of resources than lack of expertise. The opportunity to offer a program of shared continuing medical education -- The availability of medical journals and funds to attend conferences have been very limited in Bosnia since the war. We were thus surprised to find that this initiative was greeted with little enthusiasm. The reasons for this were unclear, but may have included local resentment at being perceived as requiring "education" by SFOR, or simply inappropriate subject material or difficulties in communication. There was also, at times, substantial tension in meetings of doctors from each of the three ethnic groups. Equal treatment for all patients -- The civilian clinic in Sipovo was ostensibly open to patients of all ethnic backgrounds. However, many Muslims preferred to seek treatment in the Muslim-Croat Federation rather than in Serbian Sipovo, if this was within their means. Also, we were told that a complex system of social security meant the local clinic received less money for treating Muslims, who were funded by the Federation rather than the Republika Srpska. The Western medical ethic of treating all patients equally, even in a military context, is often not applied by local doctors in countries where peacekeepers are deployed. This bias can persist long after the conflict has ceased. A foreign medical presence has an obvious benefit to groups not adequately served by local doctors, and may encourage displaced people to return to the community. In fact, there was little to suggest any ethnic bias in the doctors in our region. Deliberate ethnically motivated malpractice after a conflict can be difficult for peacekeepers to detect. The presence of a military hospital may allow identification and even prevention of such malpractice. During our prolonged deployment, we destroyed our drugs and consumables when they were out of date, even though the civilian clinic could have made excellent use of them. The ethics of supplying expired medical supplies in such situations have been discussed in recent literature.3,4 There have been accusations that Western doctors are merely shifting the cost of destroying (often inappropriate) expired drugs to the recipient. Conversely, it is argued that drugs can be put to good use if properly selected. We felt we could not donate substandard supplies. Potential benefits to the military hospital in aiding the civilian population Justification of expenditure -- Humanitarian aid does not only benefit the recipient. Military forces are always under pressure to justify their expenditure, and few things do this more effectively than having peacekeepers appear on television dispensing aid. Opportunity to exercise skills and derive a sense of achievement -- Less cynically, military personnel usually genuinely want to help. Providing humanitarian assistance allows them to put skills into practice and fosters a justifiable sense of achievement. Fostering goodwill and support among the local population -- There is also a benefit to the peacekeeping mission as a whole. The population is more likely to be supportive if they can see the peacekeepers as an indispensable force for good. This was the Australian experience at the Medical Support Force in Rwanda in 1994,5 in a situation where security was much more obviously threatened than during our time in Bosnia. Potential disadvantages of a foreign military medical presence Creation of a culture of dependency -- A prime objective of most peacekeeping operations is to restore the community to a state of peaceful self-sufficiency. To replace local medical resources with those from overseas, whether civilian or military, fosters a culture of dependency. Many temporary aid programs have fallen into this trap, with ever-increasing requirements for financial support and little improvement in the overall standard of living for the people being "helped". This is perhaps the most important reason why we attempted to restrict our humanitarian medical activities. Many non-government agencies have already left Bosnia for fear of creating dependency.6There is a conflict between the clinical imperative to treat the presenting patient, and the public health imperative to think of the welfare of the society. The rejection by aid agencies of the offer by 300 ophthalmologists to travel to developing countries to undertake cataract surgery is a well documented example7 which parallels many of the issues we faced. This decision was based largely on the notion that international assistance should build countries' capacities to deal with their own problems, with the knowledge that aid money will eventually be diverted to more visible needy causes. It was accepted that this long term view would come at the expense of many individuals who would remain blind. In addition to this central issue, there were a number of less obvious reasons why we did not encourage more direct humanitarian work. Bosnian society has not only undergone the trauma of war, but a dramatic change from a communist to a democratic system. A major theme of our programs was to encourage ordinary people to pressure their own government for improvement -- a foreign concept only 10 years ago. To provide free First World hospital treatment would have worked against this objective -- why should local people work for improved locally provided healthcare if they are given excellent foreign health facilities with minimal effort? Creation of a vacuum of resources and skills -- One principal SFOR objective is to ensure there is no "vacuum" left when NATO departs. The Bosnian government is unlikely to have the resources to provide a surgical hospital in Sipovo, so, short of seeing no civilians, we can not achieve this objective. Further, the Bosnian government may not allocate appropriate healthcare resources to the region while our hospital is present. We may also be creating a vacuum in skills when we leave, as there has been an understandable tendency for local doctors to refer patients with more complex problems to our hospital. Over time this must reduce the expertise of local healthcare personnel in managing these cases. Questions of standard of care -- The ophthalmologists referred to earlier felt bound to offer the highest standard of treatment, while many of the aid agencies favoured cheaper alternatives which could be more universally applied. The implication that an inferior procedure was "good enough" for the target population invited criticism. However, in our case, running a large primary care and tertiary referral system to Western standards could have created long term problems, as "best practice" drugs may not be available after we leave. Should we have used different standards of care for Bosnian civilians and military patients? The practice of rotating military part-time consultant doctors for short periods may be necessary, but can result in less than optimal care, as doctors are often not around to see delayed complications. Indeed, many humanitarian organisations avoid the use of volunteer doctors on brief tours in the belief that this can foster poor medical practice. Fortunately, we did not see military doctors delivering a different standard of practice to that at home -- perhaps we are becoming more skilled at working in such a setting. Adverse effects on the status of local doctors -- Patients regarded our hospital as superior to any of their civilian facilities, even in specialty areas where this was plainly not the case. As highly educated members of their community, many local doctors hold positions of significant power, both formally and informally. There is the risk that if their medical services are superseded by our First World facilities, their influence in the community could diminish, destabilising the somewhat fragile order which has been re-established since the end of the war. In more tangible terms, the incomes of local practitioners may be eroded if our presence renders their services redundant. Antagonising community leaders in this way is not sound strategy for a foreign peacekeeping force. This is why, in all but emergency cases, we only saw patients if they had a referral note from their local doctor. Potential for abuse of the system by local doctors -- There is a risk such a referral system may be abused. It would be easy to simply scribble an unintelligible note and charge the patient the full fee while taking only a brief history and no responsibility. Local doctors could also abuse this role by charging an exorbitant fee for giving access to the elective surgical resources of the military hospital. Fortunately, we had no evidence that this was occurring in Sipovo. Unrealistic expectations -- The presence of a foreign military hospital may raise the expectations of a poor community to an impossibly high level. Disappointment may result for many reasons -- lack of resources, lack of appropriately trained doctors, or simply an impossible clinical problem. Local populations often do not appreciate that a military hospital is equipped only for conditions likely to affect young, fit soldiers, and that many chronic health problems of civilians will be outside the expertise of military staff. When combined with a lack of knowledge of local medical practices and resources, and the difficulty of follow-up for civilians living far from the hospital, the standard of care delivered may be inferior to that available locally. Impossibly high expectations can also have medicolegal consequences. Refugees treated for war wounds immediately after a conflict are unlikely to want to sue the treating doctor. However, five years after the conflict, a civilian who perceives he is the victim of a doctor's poor judgement may rightly contemplate seeking compensation. Should a patient be eligible for the same award of financial damages as a patient treated in the surgeon's home country? Or is the expected standard of care different? Inadvertent attraction of skilled locals into unskilled employment -- This was a definite negative effect of our presence in Sipovo. We employed tradesmen and cleaners from the local population. Our cleaners were paid around 600 deutschmarks (A$500) per month. Some would criticise this as exploitation of cheap labour, but a doctor in the local clinic earned only 500 deutschmarks, and a teacher much less. Inevitably, we removed many educated Bosnians from jobs essential to their society's reconstruction. Obstacles in aiding the civilian population Language -- The most obvious obstacle we faced was language. We were in a largely Serbian area, and our interpreters were young Serbs. Nonetheless, our interpreters were accused of favouritism and corruption, for example in negotiating offers of employment. If the local population had been more ethnically mixed, these problems could have been magnified. Persistent antagonism between patients from different sides of the former conflict -- Fortunately, this was not a problem in our hospital, as we were in a predominantly Serbian area and much of the animosity caused by the war had diminished. One could imagine former combatants accommodated in adjacent beds might add to the list of problems usually encountered by ward staff. Limits to the number of civilians able to be treated -- It is tempting to forget the real reason for the spare capacity in a hospital such as ours -- to be able to cope with a sudden large influx of military casualties. It is most important not to fill a ward with elective civilian surgical patients who can not be discharged rapidly if necessary. Conclusions There are striking parallels between the medical and public health situation in Bosnia at the end of the 1992-1995 war and the current situation in East Timor.8 Although many of the issues faced in Bosnia are specific to a relatively developed country, the decisions about how best to assist the East Timorese are equally critical. It is instructive to note that, despite an initial fear of creating dependence in Sipovo, we were allowing increasing use of our hospital by the local civilian population. This may be inevitable when clinicians, trained to treat all who present, are cast in the role of gatekeepers. If governments are truly committed to the principles of long term development rather than fostering dependency, there seems little alternative other than to take these decisions from the hands of those who traditionally act as advocates for individual patients. Acknowledgements I thank Lieutenant Colonel N Strowbridge, RAMC, Captain B Bowman-King, QARANC, and Dr Rajko Todorcevic for their assistance in gathering information for this article. References Hovey G. The rehabilitation of homes and return of minorities to Republika Srpska, Bosnia and Herzegovina. Forced Migrat Rev 2000; 7: 8-11. Thornton R, Cordell RF, Edmonds KE. Humanitarian aid operations in Republica Srpska during Operation Resolute 2. J R Army Med Corps 1997; 143: 141-145. Berckmans P, Dawans V, Schmets G, et al. Inappropriate drug-donation practices in Bosnia and Herzegovina, 1992 to 1996. N Engl J Med 1997; 337: 1842-1845. Hoehn JB. Inappropriate drug-donation practices in Bosnia and Herzegovina [letter]. N Engl J Med 1998; 338:1472-1473; discussion 1473-1474. Ramsey W, Bridgford LR, Lusby RJ, Pearn JH. The Australian medical support force in Rwanda. Med J Aust 1995; 163: 646-651. Bower H. Divided health is a minefield for Bosnia-Herzegovina [news]. Lancet 1997; 350: 1011. Gray BH. World blindness and the medical profession: conflicting medical cultures and the ethical dilemmas of helping. Milbank Q 1992; 70: 535-556. Plan of action for humanitarian health assistance and public health action in response to the crisis in Timor. Geneva: World Health Organisation, 2000. Authors' details Nuffield Department of Anaesthetics, University of Oxford, England. Michael C Reade, MB BS(Hons), BSc(Med)(Hons), Captain, Royal Australian Army Medical Corps (attached as Medical Officer, 16 Close Support Medical Regiment, Royal Army Medical Corps, Bosnia-Herzegovina, July-August, 2000). Reprints: Dr M C Reade, Clinical Research Fellow, Nuffield Department of Anaesthetics, University of Oxford, Radcliffe Infirmary, OX2 6HE, England. michael.readeATbrasenose.oxford.ac.uk Make a comment

Michael C Reade

Cracking the Code Milestones in the Human Genome Project: genesis to postgenome Ronald J A Trent The Human Genome Project (HGP) will change medicine and medical research irrevocably. The obvious gains in genetic knowledge from the HGP, together with the advances which will flow into bioinformatics, biotechnology and the potential for novel therapeutic agents, will ensure that the financial investment in the HGP is repaid many times over. The HGP's costs in terms of ethical and social issues remain to be determined, but it is to be hoped that these will not detract from the scientific and medical achievements. How did such an endeavour start, and what path did it follow? A key player in the formative years of the Human Genome Project (HGP) was the United States Department of Energy (DOE). The DOE had a long term research focus on DNA because its early involvement in the World War II program that produced the atomic bomb had led to an interest in induced mutations. To understand the link between DNA and induced mutations, the DOE ultimately needed to characterise individual differences in DNA sequences. However, at the time, the sequences of only a few selected genes within the genome were known. Most of the estimated 40 000 human genes had yet to be discovered,1 and a considerable proportion of the 3 x 109 base-pairs making up the human haploid genome did not contain genes (about 30% is repetitive DNA2). Therefore, vast tracts of DNA with unknown function remained to be explored. A concerted effort to sequence the entire human genome within a reasonable time frame required the development of better technology. In addition, no research group was big enough to take on such a mammoth task. Despite the enormous obstacles, the majority of scientific opinion by the end of the 1980s was that sequencing the entire human genome was feasible. However, not all scientists were convinced -- there was considerable apprehension that it was a monumental exercise in data gathering rather than "true" research. There were also fears that the potential huge costs of the HGP would divert funds from more traditional research. Ultimately, the HGP, started in late 1990, was planned to be completed by 2005, and had a budget of US$3 billion. Politically, the HGP promised more than medical benefits -- it promised technological developments that would lead to economic wealth and job creation. David Smith, then Director of the DOE's Human Genome Program, described the HGP as "developing an infrastructure for future research". In reply to concerns about the potential for shrinking research funds in other areas, Smith said that, after the HGP was completed, "individual investigators would do things that they would never be able to do otherwise".3 A final point to note about the HGP is that the term "human" is a misnomer, as parallel work was also planned to sequence the genomes of model organisms, including a mouse, a fruit fly, various microorganisms, a worm, a plant and a fish. This work, called "comparative genomics", was undertaken to facilitate understanding of the human genome, as there are many similarities between human genes and those of other organisms (Box 1). Years 1-5 The goals identified for the first five years of the Human Genome Project are described in Box 2.6 During this time, many laboratories throughout the world carefully constructed maps of the genome, and then identified, by DNA sequencing, each base in the segment they were allotted. The HGP became a truly international endeavour, with the British and French participating early. Interestingly, in both countries, substantial funding for HGP-related activities came from outside the public purses (the Wellcome Trust, in the UK, and the Muscular Dystrophy Association, in France). Although the DOE was a key leading player, it was soon partnered by the National Institutes of Health (NIH). Today, the NIH is the leading public-sector player in the HGP. The Human Genome Organisation (HUGO) was formed to coordinate international efforts, as well as to facilitate education and rapid exchange of information. Australia has played a key role in HUGO, with Professor Grant Sutherland, from Adelaide, being one of the presidents of that body; the 1999 Human Genome Meeting (HGM'99) was held in Brisbane. Years 6-10 In contrast to the relatively low-key and steady progress made in the early stages of the HGP, more recent years have been considerably more turbulent. By 1998, the impressive developments in DNA-sequencing technology, particularly automation, had brought forward the timing for specific goals -- it was now believed that the complete sequence of the human genome would be determined by 2003. The first success stories of the HGP centred around the completed sequencing of genomes from model organisms (Box 3). These successes increased the momentum of the human genome work, as they confirmed that genomes could be completely sequenced, and that the information obtained had both scientific value, and potential medical importance. As the pace quickened towards the 10th year, so did the growing influence of the commercial sector (Box 3). As shown in Box 2, key goals of the HGP were the development of technology (particularly in relation to DNA sequencing), and the transfer of HGP outcomes into the private sector. The HGP represented an ideal venture in which the public and private sectors could cooperate (and compete). Governments and public funding bodies set aside substantial resources to participate in the HGP as part of the intellectual pursuit, but also as a base for economic development or alternative research funding. Developments coming from HGP were meant to be rapidly disseminated to users, an aim which would later come under some pressure. The HGP's goals requiring that DNA sequencing results were to be communicated freely and without delay were, to some extent, at odds with the protection of intellectual property through patenting. In 1991, the NIH was embroiled in an international controversy when it attempted to patent anonymous DNA sequences (those for which no function was known). Following public and international indignation, the NIH withdrew these patents.7 However, apart from the patent issue, free-flowing, publicly available information remained the rule rather than the exception, until the private sector became a major player. A high profile example of commercialisation came in the late 1990s with Celera Genomics, a privately funded organisation sponsored by Applied Biosystems (now PE Biosystems). Celera (company motto, "Speed matters") took on the might of the NIH and the world when it publicly boasted that with its resources (300 of the most modern automated DNA sequencers, and supercomputers second only to those in the US military), and a different strategy for sequencing DNA, it would finish the first draft of the human sequence before the NIH or other countries, and at a much reduced cost of US$200 million.8,9 This challenge had some positive effects, as it focused the cumbersome and slow-moving multicampus, multinational Human Genome Project, but, on the negative side, it once again highlighted that big corporations and big money can get there first, but at a cost -- the availability and access to future databases would no longer be free, at least in the short term. A new era In June this year, President Clinton, flanked by Dr Francis Collins of the NIH and Dr Craig Venter of Celera, announced simultaneously with the UK's Prime Minister Blair that the first draft of the human DNA sequence was now complete, having reached this stage with input from both the public and private sectors. Whether Celera or the NIH-sponsored initiative won the "race" is less relevant than who will control access to the databases containing the DNA sequences. At this stage, Celera appears to hold the upper hand, and is well on its way to the stated goal of being the definitive source of genomic and related medical and agricultural information.9 Although the HGP has officially reached its goals, it is important to note that this is only the first draft of the DNA sequence, and considerable work remains to ensure that DNA sequencing errors are removed. This will take a few more years. At the end of the HGP, the DNA sequence from the human genome will be deposited in various databases. What will be left is the mammoth task of working out the function of the genes. Hence, the post-genome era has been called functional genomics, which includes proteomics -- the technology and strategies required to determine the function of proteins. How this will be accomplished remains to be determined, but new technologies will be needed. The use of microarrays (a method by which the expression of many thousands of genes can be identified very rapidly with microchips) is an early, promising strategy in functional genomics. Bioinformatics will need to come up with more sophisticated programs by which the function of genes can be predicted. The traditional "wet-lab" approach to research might even give way to a complete "in-silico" (ie, computer) strategy! The first challenge -- sequencing the genome -- has been accomplished. Many more even larger challenges await us as we set out to determine the function of all human genes.10,11 References Aparicio AJR. How to count . . . human genes. Nat Genet 2000; 25: 129-130. Mueller RF, Young ID. Emery's elements of medical genetics. 10th ed. Churchill Livingstone, Edinburgh, 1998: 15. Smith D. Evolution of a vision: genome project origins, present and future challenges and far reaching benefits. Human Genome News 1995; 7: 3-4. (See <http://www.ornl.gov/hgmis/> accessed November 2000) Clark MS. Comparative genomics: the key to understanding the Human Genome Project. Bioessays 1999; 21: 121-130. Collins FS. Shattuck lecture -- medical and societal consequences of the Human Genome Project. N Engl J Med 1999; 341: 28-37. Human Genome Project Information <http://www.ornl.gov/hgmis/> (accessed November 2000). Anderson C. NIH drops bid for gene patents. Science 1994; 263: 909-910. Wadman M. Company aims to beat NIH human genome efforts. Nature 1998; 393: 101. Celera. A PE Corporation business. <http:www.celera.com/> (accessed November 2000). Burley SK, Almo SC, Bonanno JB, et al. Structural genomics: beyond the human genome project. Nat Genet 1999; 23: 151-157. Van Ommen GJ, Bakker E, den Dunnen JT. The human genome project and the future of diagnostics, treatment and prevention. Lancet 1999; 354 (Suppl 1): 5-10. Authors' details University of Sydney at the Royal Prince Alfred Hospital, Sydney, NSW. Ronald J A Trent, DPhil(Oxon), FRACP, FRCPA, Professor of Molecular Genetics. Reprints will not be available from the authors. Correspondence: Professor R J A Trent, Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050. rtrentATmed.usyd.edu.au Top right-hand corner is a photo of James Watson (left) and Francis Crick (courtesy of A Barrington Brown, Sciences Source/Photo Researchers). ©MJA 2000 Make a comment GA_googleFillSlot("eMJA_Footer728x90"); Home | Issues | MJA shop | My account | Terms of use | Terms and Conditions | MJA Careers | More... | Contact | Topics | Search | RSS mja.com.au | The Medical Journal of Australia var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-1577774-1"); pageTracker._setCustomVar(1, "access_level", "subscriber", 3); pageTracker._trackPageview(); } catch(err) {} Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 2000 Medical Journal of Australia. We appreciate your comments. 1: Comparative genomics Genes that are important to survival have been conserved during evolution, and remain common to organisms ranging from yeast to humans. For example, it is estimated that about 74% of known human genes have a corresponding homologue in the nematode Caenorhabditis elegans.4,5 This is why it is often possible to identify the function of a human gene by working on the corresponding gene in a model organism. In mice, a gene can be "knocked out" (rendered non-functional) by genetic manipulation and the effect of this observed; in fruit flies, observing the phenotypes for natural or induced mutant genes enables the function of the corresponding gene in humans to be predicted. Back to text 2: Goals of the Human Genome Project6 Identify the 40 000 or so genes which make up the human genome. Determine the sequence of the approximately 3 billion bases which make up the human genome, as well as sequencing the genomes of model organisms. Store information in databases.* Develop tools for data analysis.* Transfer technologies to the private sector. (Private industry needed to be involved to make both technology development and research training effective.) Address the ethical, legal, and social issues arising from the HGP (approximately 3%-5% of the Department of Energy/National Institutes of Health budget was directed to this goal). * These goals would require very sophisticated bioinformatics capability, so the rapid development of bioinformatics (a discipline involving computational skills) has been a by-product of the HGP. Back to text 3: Landmarks on the road to realising the Human Genome Project Date Scientific achievement/Implications 1954 Watson and Crick describe the double-stranded nature of DNA. The beginning of "molecular medicine", as diseases could now be considered in molecular (DNA) terms. 1975 Sanger, Maxam and Gilbert describe how DNA can be sequenced. This would enable the human genome to be read base by base. 1985 Mullis and colleagues describe how DNA can be amplified with the polymerase chain reaction (PCR). PCR opened up the potential for diagnosing genetic disorders. 1987 Automated means by which DNA can be sequenced becomes available through the Applied Biosystems company (later PE Biosystems). Automation allowed sequencing of large segments of DNA. This was a critical development without which the Human Genome Project could not have been conceived. 1990 Human Genome Project starts. 1991 Controversy as the NIH attempts to patent anonymous DNA sequences. New genome research centres develop as start-up, for-profit companies. The private sector is involved because of the potential for DNA diagnostics and novel therapies based on DNA sequencing data. The human genome work becomes increasingly commercialised, with the potential for future ethical dilemmas in terms of access. 1995 The DNA sequence for the genome of the first model organism (Haemophilus influenzae) is published. This is achieved by TIGR, a company with commercial ties. Craig Venter from TIGR would later form Celera. In the next three years, the genomes for model organisms Escherichia coli, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans are sequenced. The potential to understand pathogenicity at the DNA level would identify targets for novel therapeutic agents. 1996 Altruistic public policy reaffirmed that information coming from the Human Genome Project will be deposited in public databases within 24 hours. This response to the increasing influence of the commercial sector is an attempt to assuage fears among the more conservative researchers. However, with industry becoming involved, the user (government or individual) must eventually pay. 2000 The complete sequence of the fruit fly (Drosophila melanogaster) genome is announced by Celera and, as a sign of good faith, the company deposits the sequence in a public database. The first draft of the human sequence is announced by President Clinton. To date, knowledge of the DNA sequence has had a modest impact on medical practice, apart from increasing the potential for diagnosis of genetic disorders. However, with the functional genomics era will come novel therapeutics based on knowledge of DNA and its role in disease. Access to the Celera human database (as well as the mouse genome sequence due for completion soon) becomes available but only by subscription. The NHMRC is one of the first to subscribe to the Celera databases, allowing Australian scientists access to DNA sequence information not available in the public databases. Back to text Further historical information on the Human Genome Project can be found at the following web sites: http://www.ornl.gov/hgmis/ (the DOE version); http://www.gene.ucl.ac.uk/hugo/ (HUGO's role); http://www.nhgri.nih.gov/ (NIH information); http://www.fplc.edu/risk/vol5/spring/cookdeeg.htm (historical summary by Robert Cook-Deegan).

The Research Enterprise Exploring the unknown: the challenges of a career in biomedical research Gordon L Ada Gordon Ada reminisces on his career as a researcher and a facilitator MJA 2000; 173: 612-615 Getting started - Walter and Eliza Hall Institute, Melbourne - John Curtain School of Medical Research, Canberra - World Health Organization, Geneva - Retirement projects - The take-home message? - References - Authors' details - - More articles on Immunology and allergy The attractions of a career in research are many, but first among these is the opportunity to be involved in important discoveries, either personally or though close association with other researchers. Experimenting first with viruses and then in immunology at the Walter and Eliza Hall Institute (1948-1968) was a great start. Later, by becoming head of a world-class microbiology department at the John Curtin School of Medical Research at the Australian National University, I was able to establish an environment that spawned important discoveries in medical science. Getting started I had a happy childhood. I was the fourth in a family of six children -- three boys and three girls. My father studied electrical engineering at Sydney University and later became a senior executive with the New South Wales Railways, but my mother had to leave school early when her mother died. When I entered Sydney University in 1940, my aim was to study biochemistry, having received a fascinating book the previous Christmas -- The science of life, by H G Wells, Julian S Huxley and G P Wells. My years at university might not have been so enjoyable if Jack Still had not returned to Sydney University in 1941 from Gowland Hopkins' Biochemistry Department at Cambridge. He enthused us with stories about the exciting research being done there. My first research position at the Commonwealth Serum Laboratories (CSL) (1944-1946), studying ways of stabilising human serum and avoiding denaturation, convinced me of the need for new techniques to isolate and study individual proteins. I applied for leave from CSL to work at the National Institute of Medical Research in London, where moving-boundary electrophoresis and ultracentrifugation were being used for this purpose. This request, although supported by the Director of CSL, Frederick G Morgan, was refused at a higher level, so I resigned, travelled to England, and worked unpaid at the Institute with Arthur S McFarlane, Head of the Biophysics Department. After a few months, McFarlane recommended my paid appointment to the research staff. Walter and Eliza Hall Institute, Melbourne In the early 1940s, Macfarlane Burnet, Director of the Walter and Eliza Hall Institute (WEHI), on a visit to Harvard University to give the Dunham Lectures, saw the need for his institute to gain these new techniques for studying proteins. He obtained a government grant of £20 000 to establish the technologies (including, later, electron microscopy) at the WEHI. As there was no expertise in Australia, Burnet invited me to join the staff at the WEHI and, with the senior biochemist, Henry Holden, to set up moving-boundary electrophoresis and ultracentrifugation. I arrived back in Australia in August 1948. Fortunately, Holden did much of the establishing and I was able to spend most of my time on research. I became a virologist, working mainly with influenza and later Murray Valley encephalitis viruses, studying their composition and biological properties. I crystallised the Vibrio cholerae neuraminidase. In 1957, after publication of his clonal selection theory,1 Burnet decided to phase out virology in favour of immunology at the Institute. In 1962, I decided to make the switch and, after much reading, began studying immune responses, in particular the fate of tiny amounts of antigen (using the highly immunogenic Salmonella flagella and flagellin labelled with radioactive iodine) to establish the nature and location of cells which bind antigen. Because of my general ignorance of this field, I asked Gus Nossal, then the Deputy Director (Immunology) at the Institute, to help me get started. He kindly agreed, but, when the first autoradiographs showing localisation of antigen over rat primary lymphoid follicles (Box 1) were so striking, Gus decided to collaborate full-time. When presented at a meeting in the United States, our findings ranked a column in the New York Times. The next six years studying the fate and role of antigen during primary and secondary immune responses were like a taste of researcher's heaven, and Gus was a great colleague. We studied the role of antibody in antigen localisation and demonstrated the absence of antigen in antibody-forming cells. Burnet later wrote: What I can be certain about however, is the immense importance of the work on the cellular localisation of antigen led by Ada and Nossal in the 1962-5 period.2 All these findings, together with studies on the influence of antigen structure on immunogenicity with a new PhD student, Chris Parish, were published individually and then finally woven into a monograph.3 John Curtain School of Medical Research, Canberra Despite the attractions of working at WEHI, an invitation to head a department with an international reputation in virology was too exciting to refuse, and in 1968 I succeeded Frank Fenner as Head of the Department of Microbiology at the John Curtin School of Medical Research. Although much was known about the humoral response to viral infections, knowledge about cell-mediated immune responses was almost non-existent. I reasoned that research projects combining both virological and immunological approaches, supported by basic research in both these fields, would surely lead to some exciting findings. This turned out to be the case. For example: In 1972 Chris Parish was the first to show the inverse relationship between antibody and cell-mediated immune responses, which led others to describe two classes of helper T cells. Bruce Stillman's studies on adenovirus in 1978 started him on the road to becoming Director of the renowned Cold Spring Harbor Laboratories in New York State. Robert Blanden was to lay the foundations for a major finding. Our department was acknowledged as a world leader in poxvirus research,4 and Blanden was studying the immune response to ectromelia, a poxvirus pathogenic for mice. In the next few years, using technology for assaying the newly discovered cytotoxic T cells gleaned from overseas meetings, Blanden, in late 1972, became the first to show that cytotoxic T cells would kill cells infected with ectromelia virus. But how did these cells recognise virus-infected cells? Early indications were that major histocompatibility (MHC) antigens were involved in some way, so some inbred mouse strains (members of the same strain having identical MHC antigen specificities) were imported to facilitate further studies. Peter Doherty came to the department as a postdoctoral fellow in 1972, and started work on lymphocytic choriomeningitis (LCM) virus infections of mice. In early 1973, Rolf Zinkernagel, a Swiss medical graduate, worked for a while with Blanden to learn about assaying cytotoxic T cell activity. I then asked Doherty and Zinkernagel to share the same laboratory, as they clearly had similar research interests. In some very elegant experiments, they found that cytotoxic T cells formed during an LCM viral infection would only lyse infected target cells if effector and target cells shared at least some MHC antigen specificities (ie, the T cell lytic activity was "MHC restricted"). They suggested that the cytotoxic T cell receptor recognised at the infected cell surface some virus-induced alteration of the MHC molecule, possibly caused by complexing with a viral antigen.5 They proposed the fundamental concept -- that a central function of MHC antigens on cells was to signal changes in "self", to what they now called "altered self", to the immune system.6 Once identified, such a cell would be lysed. This finding stimulated much research both in the department and elsewhere, and studies investigating the details of MHC restriction of T cell responses became a leading immunological topic internationally. Needless to say, Zinkernagel was awarded a PhD scholarship and graduated in record time. Both he and Doherty left to work overseas in the mid-1970s. Subsequently, analysis of crystals of MHC molecules, isolated from the surface of infected cells by US researchers, showed a viral peptide occupying a cleft in the MHC molecule so that parts of each were recognised by the cytotoxic lymphocyte receptor (Box 2). The award of the 1996 Nobel Prize in Physiology or Medicine to Rolf Zinkernagel and Peter Doherty (Box 3) recognised the importance of their original discovery, as it was the first description of the molecular mechanism used by vertebrates for the control and clearance of most intracellular infectious agents, especially viruses. World Health Organization, Geneva For 20 years, from 1971, I became associated with different World Health Organization programs, concerned mostly with the development and use of vaccines (Box 4). I was the first Chairman of the Programme for Vaccine Development (1984-1989), which is now a much larger WHO program with Gus Nossal as Chairman. These experiences focused my own research towards defining the roles of different components of the immune response to viral infections. Retirement projects As I approached retirement (December 1987), I was invited to do a six-month consultancy at WHO (to plan for a major review of studies on developing a vaccine to control pregnancy in women), to spend my retirement at Johns Hopkins School of Hygiene and Public Health in Baltimore, and to give the plenary lecture on The prospects for HIV vaccines at the Fourth International AIDS Congress in Stockholm in May 1988. I had never worked with HIV, but the Swedes apparently wanted an "independent" opinion. Stockholm By 1986, HIV RNA had been largely sequenced, and there was great optimism that a vaccine could be developed quickly. However, in the next two years, several disturbing findings were made, especially the very great sequence variation of the envelope antigen in different HIV isolates. There are three desirable properties of an infectious agent which can facilitate vaccine development (Box 5). At the Stockholm lecture,7 I listed seven reasons why it would be very difficult to develop an HIV vaccine based primarily on strong infectivity-neutralising antibody formation (Box 5). I then drew on recent research by two of my colleagues, David Boyle and Ian Ramshaw, at the John Curtin School of Medical Research. They had shown that DNA, coding for antigens of other infectious agents and of cytokines, could be inserted into the DNA of a poxvirus, such as vaccinia virus. Vaccination with this "chimeric" virus could protect against infection by the agent which was the source of the inserted DNA. I therefore suggested that, because the internal antigens of HIV (which are the source of many T cell epitopes) showed considerably less variation, a vaccine might be developed based on vaccinia virus containing the genes coding for the internal HIV antigens, gag and pol, as well as for the cytokine, interferon gamma.7 In mice, such a construct generated a strong cytotoxic T cell response; in man, this might be sufficient to better control, if not clear, an HIV infection. The 8000-strong audience was largely stunned by my assessment of the situation, although none subsequently disputed it. However, major vaccine manufacturers ignored it, determined to make an antibody-inducing subunit vaccine based on the HIV envelope antigen, a strategy driven by the success of the hepatitis B viral vaccine which contains the surface antigen of that virus. Baltimore and Washington On arrival in Baltimore in July 1988, I was warmly welcomed, made Associate Director of a new Center for AIDS Research and later became Director. In Washington, I was asked to participate in meetings and activities of the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Disease. In 1991, after three years in the United States, my wife and I decided to return to Australia, but I was invited to continue the relationship with DAIDS and to join a new HIV Vaccine Working Group. The crunch came in 1995, when the Director of the US National Institute of Allergy and Infectious Disease refused to support a Phase III clinical trial of the then leading HIV candidate vaccine, based on the envelope antigen. Many reasons were given, but two critical ones were: Antibody from volunteers immunised with this candidate vaccine did not prevent infection by newly isolated HIV field strains; and The vaccine did not induce cytotoxic T cell formation in the volunteers. This was a major turning point in international HIV vaccine research. The National Institute of Allergy and Infectious Disease completely revamped its HIV vaccine development program, and my hectic travel schedule to and from the United States came to an end. My last task for the Working Group was to review the evidence supporting a role for cytotoxic T cells in controlling HIV infections.8 Return to Canberra In 1991, I was appointed Visiting Fellow in the (now) Division of Immunology and Cell Biology at the John Curtin School and Chairman of the HIV Vaccine Working Group, one of the committees of the National Centre in HIV Epidemiology and Clinical Research in Sydney. Ian Ramshaw had recently shown that a vaccination schedule involving priming with plasmids containing DNA coding for selected antigens, followed by boosting with chimeric fowlpox virus coding for the same antigens, gave a greatly enhanced immune response in mice. Stephen Kent (now at the University of Melbourne) and Ramshaw and their colleagues showed that Macaca nemestrina monkeys immunised in this way developed a strong cytotoxic T cell response and rapidly cleared a subsequent HIV infection.9 Any antibody induced was irrelevant. Supporting findings for this approach were later reported from the United States. Now Australia was set to develop an HIV vaccine initiative based on this vaccination technology. At a meeting of the HIV Vaccine Working Group, David Cooper, Head of the National Centre in HIV Epidemiology and Clinical Research, was elected to head an Australian HIV Vaccine Consortium. In June this year, out of 20 international applications received, the National Institute of Allergy and Infectious Disease awarded four contracts, three to US groups and the fourth to the Australian consortium ($27 million over five years) to carry out clinical trials of their vaccine formulation. It is anticipated that a strong immune capability based on cytotoxic T lymphocyte activity will greatly reduce viral titres. Thus, those infected by HIV will live longer and be much less likely to infect others. If this vaccination technology can be shown to generate strong cytotoxic lymphocyte responses in humans, it heralds a new approach to controlling other difficult infectious diseases, such as malaria, trachoma and pelvic inflammatory disease, and even pandemic influenza. The take-home message? From a career path in biochemistry, I switched to virology, then to immunology and became an enthusiastic supporter for the application of immunisation technology, not only for the more difficult infectious diseases but also for non-communicable diseases. Young researchers should jump at the chance to switch fields when exciting opportunities arise. Acknowledgement: I wish to acknowledge with gratitude the great support of my wife, Jean Ada, during my career. References Burnet FH. A modification of Jerne's theory of antibody production using the concept of clonal selection. Aust J Sci 1957: 20; 67-69. Macfarlane Burnet I. Walter and Eliza Hall Institute, 1915-65. Melbourne: Melbourne University Press, 1971. Nossal GJV, Ada GL. Antigens, lymphoid cells and the immune response. New York: Academic Press, 1971. Fenner F. Nature, nuture and my experience with smallpox eradication. Med J Aust 1999; 171: 638-641. Zinkernagel RM, Doherty PC. Restriction of in vitro cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semi-allogeneic system. Nature 1974; 248: 701-702. Doherty PC, Zinkernagel RM. A biological role for the major histocompatibility antigens. Lancet 1975; 1: 1406-1409. Ada GL. Prospects for HIV vaccines. J Acquir Immune Defic Syndr 1988; 1: 295-303. Ada GL, McElrath MJ. Perspectives. HIV type-1 vaccine-induced cytotoxic T cell responses: potential role in vaccine efficacy. AIDS Res Hum Retoviruses 1997; 13: 243-248. Kent SJ, Zhao A, Best SJ, et al. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J Virol 1998; 72: 10180-10188. Authors' details John Curtin School of Medical Research, Australian National University, Canberra, ACT. Gordon L Ada, AO, DSc, FAA, Emeritus Professor, and Visiting Fellow in the Division of Immunology and Cell Biology. Correspondence: Professor G L Ada, John Curtin School of Medical Research, P O Box 334, Canberra, ACT 2601. Make a comment 1: Antigen in the immune response Autoradiograph showing localisation of antigen over primary lymphoid follicles of rat popliteal lymph nodes, after footpad injection of Salmonella flagellin labelled with radioactive iodine. Back to text 2: The function of major histocompatibility antigens Schematic diagram of the cytotoxic T lymphocyte receptor recognition of the complex between the major histocompatibility antigen molecule and a nonapeptide derived from an infectious agent protein expressed on the surface of the infected cell. Back to text 3: At the 1996 Nobel Prize awards Evening banquet after the awarding of Nobel Prizes, Stockholm, December 1996. From left to right: Gordon Ada, Peter Doherty and Frank Fenner at the display of Nobel Prize medals and citations (photograph courtesy of Peter Pockley). Back to text 4: Involvement with World Health Organization programs 1971-1973 Member, Fellowship Selection Committee 1973-1976 Member, then Chairman (1975-1976), Scientific Council, International Agency for Research on Cancer, Lyons, France 1978-1984 Member, Scientific and Technical Advisory Committee, Tropical Diseases Research 1981-1984 Member, Global Advisory Committee on Medical (Health) Research 1984-1989 Chairman, Scientific Advisory Group of Experts, Programme for Vaccine Development. Member and later Consultant (1988), Vaccination Committee, Human Reproduction Programme 1985-1988 Member, Regional (Western Pacific) Advisory Committee on Health Research 1987-1989 Member, Research and Development Group, Expanded Programme on Immunization Back to text 5: Factors for and against the development of an effective vaccine Factors favouring the development of an effective vaccine Only one or a few strains of the infective agent exist; little or preferably no antigenic variation within a strain. Infective agent causes an acute infection; host completely recovers from a sublethal dose of the agent; agent does not persist. Agent is moderately (rather than highly) infectious. Factors militating against development of an effective vaccine (all these factors apply to HIV) Great antigenic variation; antigenic drift. Integration of viral DNA/cDNA into the host cell genome. Infection may be transmitted by cells which are latently infected. Immune enhancement: antibody can enhance infection of macrophages/monocytes if these cells are susceptible to infection. Agent infects cells in immunoprivileged sites in the host. Crucial cells of the immune system are infected, and either destroyed or their function is impaired. Failure to produce protective antibody and/or persisting cell-mediated immunity responses. Back to text

Gordon L Ada

The Research Enterprise John Kerr and apoptosis Michael G E O'Rourke and Kay A O Ellem MJA 2000; 173: 616-617 On 14 March 2000, John Foxton Ross Kerr, Emeritus Professor of Pathology at the University of Queensland, received the Paul Ehrlich and Ludwig Darmstaedter Prize for his description of apoptosis, a form of cell death. The prize, which he shared with Boston biologist Robert Horvitz, is considered to be one of the most prestigious European awards in science, second only to the Nobel Prize. John Kerr's discovery, initially called "shrinkage necrosis" but which he later renamed "apoptosis", came about in the late 1960s, when his attention was caught by a curious form of liver cell death during his studies of acute liver injury in rats. The findings of this seminal study were first published in 1965.1 Subsequently, Kerr and his co-authors (including Jeffrey Searle) described the unique morphological changes of this type of cell death, compared with those of necrosis, in a series of articles published during the 1970s and 1980s.2-4 These studies extended the range of pathological and physiological states in which apoptosis is known to occur. Further studies with other collaborators (who later included Alastair Currie and Andrew Wyllie)5 led to an increase in the understanding of the role of apoptosis in embryogenesis, spermatogenesis, cancer growth, and tissue remodelling during healing or functional regression. At first thought to be somewhat arcane as a topic, the literature on apoptosis initially grew slowly. However, recognition of the significance of this "protected" form of cell death on immune function and regulation was followed by an explosion of related publications in immunology. Biochemists now recite a mantra of enzymes involved in apoptosis, and chant a list of factors capable of modulating or regulating its expression. It has become de rigueur to adorn seminars and lectures with charts of the increasingly complex interactions which occur between signalling pathways as they are traversed by the informing reactions (which either trigger or defuse the suicidal steps leading to apoptotic cell death). The astonishing total number of publications on apoptosis is now over 35 539, including some of the world's leading scientific journals, such as Nature6-8 and Science.9-11 Apoptosis is now a growth industry, the clinical implications of which can be applied to chemotherapy, the endocrine treatment of cancer, autoimmune disease and neurodegenerative disease. This body of evidence is a tribute to the catalytic influence that John Kerr's insights have had in so many disparate disciplines and areas of biological study. These insights revealed the importance of this process as a universal microphenomenon in the macroevents of tissue and organismal function, and in disease. References Kerr JF. A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. J Path Bact 1965; 90: 419-435. Kerr JF, Cooksley WG, Searle J, et al. The nature of piecemeal necrosis in chronic active hepatitis. Lancet 1979; 20: 827-828. Searle J, Lawson TA, Abbott PJ, et al. An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. J Pathol 1975; 116: 129-138. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol 1979; 2: 133-144. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257. Wallach D. Apoptosis: Placing death under control. Nature 1977; 388: 123-126. Hengartner MO. Apoptosis: death cycle and Swiss army knives. Nature 1998; 391: 441-442. Martinou JC. Apoptosis: key to the mitochondrial gate. Nature 1999: 399; 411-412. Barinaga M. Apoptosis: forging a path to cell death. Science 1996; 273: 735-737. Barinaga M. Apoptosis: death by dozens of cuts. Science 1998; 280: 32-34. Brenner C, Kroener G. Apoptosis: Mitochondria -- the death cell integrators. Science 2000; 289: 1150-1151. Cotran R, Kumar V, Collins T, editors. Pathological basis of disease. 6th ed. Philadelphia: W. B Saunders, 1997: 18-24. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994; 73: 2013-2026. Walker NI, Harmon BV, Gobe GC, et al. Patterns of cell death. Methods Achiev Exp Pathol 1988; 13: 18-32. Sandford N, Searle JW, Kerr JF. Sucessive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation. Pathology 1984; 16: 406-410. Soubrane C, Mouawad R, Antoine EC, et al. A comparative study of Fas and Fas-ligand expression during melanoma progression. Br J Dermatol 2000; 143: 307-312. Andrane F, Casciola-Rosen L, Rosen A. Apoptosis in systemic lupus erthymatosus. Clinical implications. Rheum Dis Clin North Am 2000; 26: 215-227. Make a comment John Kerr (right) with Roland Koch, Prime Minister of Hesse, Germany, and Honorary Chairman of the Board of Trustees of the Paul Ehrlich Foundation, at a dinner for award recipients. 1: Other awards and lectures recognising John Kerr's achievements Keynote opening addresses at the Cold Spring Harbor, New York, Symposia, 1990. Opening lecture, The cell and molecular biology of apoptosis, at the Queensland Institute of Medical Research Cell and Molecular Biology Symposium, 1992. Opening lecture at the conference Apoptosis in AIDS, Paris, 1993. 12th Mildford D. Schultz Lecture, Harvard Medical School, Boston, 1993. Bancroft Medal (Queensland AMA), 1993. John Earnshaw Memorial Lecture, International Melanoma Conference, Brisbane, 1994. Fred W Stewart Award, Memorial Sloane-Kettering Cancer Center, New York, for contribution to cancer research, 1995. Doctor of Science honoris causa, University of Queensland, 1998. Fellowship of the Australian Academy of Science, 1998. Back to text 2: Apoptosis: programmed cell death The term "apoptosis" is derived from the Greek for "falling off" and describes a distinct form of cell death whereby cells die in a tightly regulated and morphologically uniform fashion.12 Morphologically, there is condensation of the nucleus and cytoplasm, membrane blebbing, and the formation of discrete, packaged apoptotic bodies which are phagocytosed by nearby cells, without provoking an inflammatory reaction.13 In contrast to necrosis, a degenerative process in which cells swell and lyse after irreversible tissue injury, apoptosis appears to be an active process14 which is subject to genetic regulation. Apoptosis can be triggered either from within the cell, or from outside the cell (mediated by binding of surface membrane receptors to "death activators" such as Fas-ligand and tumour necrosis factor). Electron micrograph showing apoptosis occurring spontaneously in cell culture. Note the discrete, membrane-enclosed nuclear fragments, with characteristic segregation of uniformly compacted chromatin, the crowding of well preserved cytoplasmic organelles and the marked convolution of the cellular surface, which is a prelude to conversion of the cell into a number of membrane-bound fragments or apoptotic bodies. N = nucleus, O = organelles. Apoptosis may occur in several different physiological, adaptive and pathological settings. For example, apoptosis acts as a homoeostatic mechanism for controlling cell populations, and in hormone-dependent tissue involution such as endometrial breakdown during menstruation, prostatic atrophy after castration,15 and cessation of lactation after weaning.12 Localised apoptosis plays a role in embryonic development, such as formation of interdigital clefts and involution of phylogenetic vestiges.5 In malignant tumours, apoptosis may occur spontaneously, or may increase in response to cytotoxic chemotherapy or irradiation.13 Impaired regulation of apoptosis is known to be associated with the development of various types of cancer,16 and with the pathogenesis of some autoimmune diseases such as systemic lupus erythematosus.17 Back to text

Power of One A clinician with a passion for pathology Priscilla Kincaid-Smith MJA 2000; 173: 639-642 As a woman in medicine and as a scientist, Professor Kincaid-Smith has met and overcome some determined obstructionists Hammersmith and the research focus - No place for women - Analgesic nephropathy - The achievements of pathology - References - Author's details Make a comment - - - More articles on History Introduction The early 1950s, when I graduated, were an exciting time in clinical medicine. Penicillin had only just become generally available and it revolutionised the treatment of infectious disease, particularly in a hospital like Baragwanath Hospital, where I spent my early years as a doctor. This 2000-bed hospital across the road from the now-infamous Soweto township outside Johannesburg was to absorb my full attention for the next two years. It was a very exciting place for the residents and registrars, as the wards were full of very ill patients many of whom could now be cured. A dose of penicillin which we would now consider homoeopathic transformed pneumonia into an illness lasting a few days and its mortality fell dramatically. In the same years chloramphenicol did for typhoid fever what penicillin had done for pneumonia, and chloroquine cured most patients with malignant cerebral malaria. The ward balconies were full of patients with advanced tuberculosis and this too became a curable disease after streptomycin became available. Hammersmith and the research focus After three years of working like a galley slave but gaining a huge experience in clinical medicine, I was lucky enough to be accepted at Hammersmith Hospital, London. At that time Hammersmith Hospital was a leader in many fields, notably in cardiology, where McMichael and Sharply-Schafer had pioneered cardiac catheterisation and the Australian, Paul Wood, certainly one of the world's top clinical cardiologists, worked for a time. At Hammersmith the whole attitude was to do research, and improve medical knowledge. It didn't give me the same satisfaction of saving lives, but it was certainly the academic centre of London in the 1950s. At that time the ancient traditions of the London teaching hospitals were a handicap to doing new things and research. Hammersmith was frowned upon as "that hospital next to HMP Wormwood Scrubs, that hospital where they did all those experiments!". I came into contact with some of the most famous names in medicine. Each day seemed more exciting than the last and the rate of learning was exponential. I spent two and a half years in anatomical pathology, but my research interest in hypertension and the kidney stood me in good stead for my future career in the then non-existent field of nephrology. Renal biopsy was in its infancy and Robert Heptinstall, perhaps the world's best renal pathologist, came over regularly from Mary's Hospital to look at renal biopsies with our expert in this field, "Do" Doniach, who was senior pathologist at Hammersmith Hospital. This exposure to living pathology has had a great influence on my career in nephrology, which, although unequivocally clinical, has always kept me close to a microscope and involved in pathology. As a pathology registrar, I spent the mornings doing autopsies, the highlights of which were the attendance at lunchtime of all the top clinicians for a presentation of the findings. This was a no-holds-barred school, with people like John McMichael (Head of Medicine at Hammersmith) and Sheila Sherlock (who published the first major book on hepatology and became a world leader in the field). Nothing was taken for granted: the questioners were a very erudite and exacting bunch of clinicians. Histological analyses of biopsies and surgical specimens were reported on the day they became available. This necessitated many late nights to prepare for the consultant pathologist's overview the next morning, but this one-on-one learning process was excellent. As an early riser I found that I could easily start work about two hours before anyone else arrived, which allowed me to do some research. My first "kidney" paper was published in The Lancet in 1955,1 and I managed quite a lot more in those extra two hours each day. Although I was fully immersed in pathology, I couldn't drag myself away from the wards. After attending ward rounds two or three times a week, my envy of the doctors looking after patients finally drew me back to clinical medicine in 1956. My training was in cardiology -- there was no specialty of nephrology --but, as hypertension was my main research interest and most of my previous research had involved hypertension and the kidney, I became a de facto nephrologist. Another great advantage was that Malcolm Milne was second in charge in the McMichael cardiology unit in which I worked, and he was truly one of the founding fathers of nephrology. Not only did I learn a lot from Malcolm, but we ran the dialysis service for southern England and collaborated with a string of clinical fellows with renal interests, among them Bob Muehrcke (who established renal biopsy as a safe procedure) and Belding Scribner (of dialysis fame). In 1958 Sir John McMichael called me into his office to offer me a junior consultant post at Hammersmith. I was overwhelmed and greatly honoured, but had that week become engaged to Ken Fairley (from Melbourne, who spent four years training at the National Heart Hospital in cardiology with Paul Wood), and neither of us really wanted to bring up a family in England. I sometimes wonder if, had I known what awaited me in Australia, I might not have tried to persuade Ken to stay in England after all. No place for women I had assumed that I would be eligible for a similar post in Melbourne to that offered in what I regarded as the UK's top hospital, but I was very wrong. In the 1950s, in Australia, when a woman married she automatically lost her job. I was not considered for any significant post in a hospital or university in Melbourne. My curriculum vitae was not wanting: I had published several respectable articles, held a postgraduate qualification in pathology, was a member of the Royal College of Physicians, London, and had eight years of first class postgraduate training. I had excellent references. But I was the wrong sex! I was devastated. It seemed that almost all doors were closed to married women. After doing general practice locums to help pay the bills, Sir John McMichael arranged a part-time research position for me at the Baker Institute at the Alfred Hospital, Melbourne. However, Ken and I decided that if I was not wanted in Melbourne perhaps we could be of service in New Guinea, which had almost no specialists in its health service. We applied for and were offered appointments, Ken as a physician and I as a pathologist. We went up to New Guinea to inspect the new hospital in Rabaul and were thrilled with the facilities, but soon discovered that, as a married woman, my appointment could only be temporary. If any man, irrespective of qualifications, applied, he would get the position, and permanent to boot! So it was back to Melbourne, where I was appointed as an honorary physician at the Queen Victoria Hospital, a hospital run by women for women. I also had a part time research position at the Baker Institute and a part time research and teaching appointment in the University of Melbourne, Department of Medicine, at the Alfred Hospital. Eventually, in 1967, I was appointed as first Assistant in Medicine in the University of Melbourne. That was the year in which barriers to employing married women in universities were removed. Analgesic nephropathy It was on my very first day at the Alfred that I encountered my first case of what was later called analgesic nephropathy. I went, as I always had at Hammersmith Hospital, to review that day's postmortem findings. There was no formal presentation and the pathologist seemed somewhat surprised to see me. Demonstrated were the kidneys from three patients. All showed the same lesion, a kind which I had never encountered at the Hammersmith. These had very obvious features: black necrotic papillae with overlying atrophy and with striking hypertrophy in adjacent columns of Bertin (Box 1). On asking the pathologist what this lesion was he replied that it was papillary necrosis, a common complication of renal infection. "Well, it doesn't occur in renal infection in London", I replied, but I don't think he believed me. Although I recognised the lesion as the sign of a specific disease process at that first-ever autopsy attendance in Melbourne early in 1959, it took a bit longer to connect it to analgesic abuse. I had, of course, seen acute renal papillary necrosis in an occasional kidney in England, but the Alfred cases were quite different and more chronic lesions. Phenacetin nephritis had been described in Switzerland as chronic interstitial nephritis in 1953, but there was almost no mention of papillary necrosis in the description, certainly none of pigmented papillae. When I was finally able to get a photograph of one of the Swiss kidneys it was clearly different: the kidney was small and there was a moth-eaten appearance of the papillae, which presumably represented areas from which necrotic tissue had been lost (Box 2). Ken Fairley was working in Bill King's unit at the Royal Melbourne Hospital and it was he who made the connection between the kidneys seen so frequently on the autopsy table in Melbourne and analgesics. Bill King was a busy gastroenterologist and when he encountered patients with renal disease he consulted Ken. Over a relatively short period of time Ken gathered a series of patients with peptic ulcers and impaired renal function who also had a history of a phenomenally high intake of analgesics. When one of these patients passed a small fragment of pigmented material which was processed and turned out to be a piece of renal papilla the puzzle was solved. These patients had analgesic nephropathy, even if the lesions were quite different from those described by Spühler and Zollinger in Switzerland.2 In 1963, at the International Society of Nephrology meeting in Prague, we had great difficulty in persuading our European colleagues to accept our evidence for this new form of analgesic nephropathy. They particularly did not like the large kidneys, which we demonstrated to reduce in size on radiological imaging as papillae were sloughed, with resulting cortical atrophy. This always seemed to me to be the likely pathogenesis of the so-called "chronic interstitial nephritis". They objected even more strenuously to the demonstration that this shrinkage in our cases was often followed by remarkable hypertrophy in Bertin's columns. They stressed the rarity of pigmented papillae and papillary necrosis, both major features of our cases. They argued that what we were describing was certainly not "phenacetin nephritis". We were already calling it "analgesic nephropathy" by then, because it continued unabated if patients ceased taking phenacetin and replaced it with paracetamol. There was strong opposition to this view and almost a denial of any connection between our Australian variety of analgesic nephropathy and their "phenacetin nephritis" with chronic interstitial nephritis. Later, years of careful clinical documentation and animal experimentation showed that it was not the phenacetin but the mixed analgesics that caused the renal papillary necrosis. Phenacetin alone or its immediate metabolite, paracetamol, could be fed to rats in huge quantities without causing apparent damage. But when we fed rats the analgesic powders and tablets then being sold in huge quantities in Australia we quickly reproduced the lesion of renal papillary necrosis, which closely resembled analgesic nephropathy in man, even to the detail of pigmented papillae. The stories of analgesic abuse extracted from patients at that time were incredible. The patients were truly addicted to the analgesics. They appeared to be seeking the mood-altering effects, not the analgesic effects, and it seemed that it was the phenacetin which they missed when taking different combinations. The patients were commonly heavy smokers and found it easier to give up cigarettes than analgesics! In the first group of patients that we studied, as many died of coronary artery disease as of renal failure.3 Extensive premature atheroma was a prominent feature, but we could never quite prove that it was the analgesic abuse and not the smoking that was linked to the atheroma. Renal artery stenosis was another common feature, perhaps also due to smoking, but we did postulate that the huge quantities of aspirin which these patients took may have destroyed the "good" as well as the "bad" prostaglandins and predisposed to severe atheroma. Our wards were full of patients with the analgesic syndrome. In addition to the characteristic renal disease, peptic ulceration, anaemia, premature atheroma and premature ageing, dementia was a frequent finding. Some blamed phenacetin for the impaired cognitive function. Severe and often malignant hypertension was another characteristic feature. Renal failure was of course a major cause of death, but if the patient could be persuaded to give up the analgesic abuse a remarkable degree of recovery could be expected. Nonetheless, when this condition started to feature on dialysis and transplant registries 10 years later, it was indeed a major cause of end-stage renal failure -- most common in Queensland and New South Wales and least common in Victoria, where our studies had been carried out. Gradually the message got across. Long before government regulations were introduced to control sales, people became aware of the dangers of analgesic abuse and the prevalence gradually declined. Analgesic powders and tablets, which were then available free in factories and other places, also disappeared, as did the cardboard boxes in which a gross of analgesic powders or tablets were sold. They had once been a very prominent item in the weekly family supermarket trolley. Over the next 10 years or so, the pharmaceutical companies lobbied long and hard against the evidence that analgesic abuse was a major cause of renal failure. In the late 1970s I happened to be flying interstate, seated in front of two senior executives from one of the many companies whose fortunes were founded on APC sales. From this vantage point, I overheard them vigorously attacking me and what I had said about analgesic nephropathy. I was of course delighted that they thought that I had had such an influence on analgesic sales. Later, the tenor of their discussion was that Australia was a lost cause for advertisement and sale of mixed analgesics, and they began to discuss plans to invade the markets of South East Asia, where there were no controls over either advertising or sales. They were targeting Malaysia in the first instance, and reports of analgesic nephropathy from Malaysia 10-20 years later confirm that their plans succeeded. Advertising had been one of the secrets of the success of analgesic sales and this dated back to the 1920s, when Nicholas in Melbourne commenced manufacture of aspirin after the defeat of Germany in World War I and the collapse of Bayer. History relates that a new manager from the United States had predicted that there were millions to be made from aggressive advertising of analgesics. Thirty years later one would still hear on television programs that "You will need Aspro today". It was not uncommon even in the 1960s and 1970s to see shop windows devoted to advertising a particular variety of analgesics (Box 3). Between 1979 and 1982 all Australian States legislated to control over-the-counter sales of mixed analgesics. This was 20 years after most nephrologists were convinced of the need to do this. The final success came from joint activities by the Australian Kidney Foundation and the Australasian Society of Nephrology, which managed to convince the National Health and Medical Research Council and, in turn, the Government. Progress was painfully slow to those of us struggling with the very common disease which resulted from analgesic abuse. The controls were sensible and effective. Regulations controlled the number of analgesics that could be sold in one pack and did not permit the sale of combinations of aspirin, phenacetin, paracetamol and caffeine. Analgesic nephropathy, which had been such a common clinical condition, gradually faded away. The achievements of pathology Although I now rarely visit the autopsy room, I still look down the microscope every day, peering at all the fascinating things which appear in the urine of patients with renal disease, or examining renal biopsies. I now have a collection of some 20 000 renal biopsies; in many I have known the clinical story as well as the pathology. Nephrology was at first dominated by physiologists and pathology was a very poor relation, but, in my view, pathology has contributed far more to clinical nephrology than physiology. Now pathology, in combination with various immunological techniques applied to biopsy tissue, is certainly at the forefront of advancing knowledge in nephrology. References Kincaid-Smith P. Vascular obstruction in chronic pyelonephritic kidneys and its relation to hypertension. Lancet 1955; 2: 1263-1269. Spühler O, Zollinger HV. Die Chronische Interstitielle Nephritis. S Klin Med 1953; 151: 1-50. Dawborn JK, Fairley KF, Kincaid-Smith P, King WE. The association of peptic ulceration and chronic renal disease and analgesic abuse. Quart J Med 1966; 35: 69-83. Author's details Epworth Hospital, Melbourne, VIC. Priscilla Kincaid-Smith, AC, MD, FRACP, FRCPA, Medical Director and Director of Nephrology; Emeritus Professor, University of Melbourne. Reprints will not be available from the author. Correspondence: Professor P Kincaid-Smith, Epworth Medical Centre, 185-187 Hoddle Street, Richmond, VIC 3121. priscillkATepworth.org.au 1: Autopsy specimen of both kidneys and the aorta in a 43-year-old man The kidneys show bars of hypertrophy on the outer aspect of the right kidney representing hypertrophy in columns of Bertin. The cut surface of the left kidney shows typical features of analgesic nephropathy, with black pigmented papillae, atrophy of cortex over nephrotic papillae and pale areas of hypertrophy in Bertin's columns. The aorta shows extensive atheroma. Return to text 2: Cut section of a kidney with typical features of the "Swiss" variety of analgesic nephropathy The cortex is atrophic. The papillae show small cavities from which necrotic material has been lost. No hypertrophy is seen in Bertin's columns. Return to text 3: A typical 1960s shop window display advertising a popular analgesic Return to text

Priscilla Kincaid-Smith

Letters Incongruous infants: facial features in old paintings MJA 2000; 173: 670 To the Editor: The following quote is from Sinclair's Human growth after birth: The head of the new-born baby is relatively large. This is reflected in the finding that in the infant the ratio of vertical head height to total height is 1:4, whereas in the adult it is 1:7.5. This difference was not appreciated by many well-known early European painters, and it is common to find representations of the Virgin and Child in which the baby has the chubby outline typical of his age but the proportions typical of an adult.1 I thought it would be interesting to test this statement. Most paintings of the Virgin and Child show the Virgin seated and the Child in various postures, making it impossible to measure their total height. However, we do know that the ratio of head length (vertex to chin) to forearm length (elbow to wrist) is 2:1 in the newborn, 7:4 at the age of two, and 1:1 in adults. Also, the ratio of upper head length (vertex to eyes) to face length (eyes to chin) is 4:3 in the newborn and 4:5 in adults.1 Using paintings reproduced on postcards and in the Time-Life series of art books,2 I made the appropriate body measurements of the Virgin and Child from 41 works painted between 1225 and 1619 CE. Allowing for about 10% variation in the normal ratios I obtained the following results: The head : forearm ratio for the Virgin was normal in 29 of 40 measurements; less than normal in 9; and greater than normal in 2. This ratio for the Child was normal in 12 of 41 measurements; less than normal in 25; and greater than normal in 4. The upper head : face ratio for the Virgin was normal in 18 of 43 measurements; less than normal in 15; and greater than normal in 10. This ratio for the Child was normal in 11 of 43 measurements; less than normal in 30; and greater than normal in 2. However inaccurate my measurements may be, measuring from a picture with the figures at various angles, the results do show a consistent pattern over the centuries. The artist tends to underestimate both the head : forearm ratio and upper head : face ratio in the Child. The ratios for the Virgin were also outside the normal range in many of the examples measured. Artists down the ages have always distorted the anatomical shape of their figures if they felt a better image would result. Artists who lived during the period surveyed would have had the example of the stylised and distorted forms of Byzantine art constantly before them, in the churches and monasteries in which they painted their works. When all is said and done, how important is anatomical accuracy in the production of an otherwise wonderful work of art? John E Gault Physician 203 View Street, Bendigo, VIC 3550 Sinclair D. Human growth after birth. 2nd ed. Oxford: Oxford University Press, 1973: 102-105. Time-Life Library of Art series. Time-Life International (Nederland) b.v.

John E Gault

Editorial Reconciliation, social equity and Indigenous health A call for symbolic and material change MJA 2000; 172: 468-469 The current state of health of Indigenous Australians is a cause for national shame, and has its roots in the wholesale exclusion of Indigenous people from Australian society since 1788. A comprehensive approach to improving the health of Aboriginals and Torres Strait Islanders involves understanding the close relationships between their social and economic status and their health. At some point in our growth as a nation there must be a commitment by all Australians to social and educational equity and economic prosperity for Indigenous Australians. Only then will there be significant improvements in the health of Indigenous Australians. There is a growing body of knowledge about the social determinants of health,1-3 and evidence that relates disease patterns to the organisation of society and the way society invests in its human capital. Evidence worldwide shows a clear relationship between poverty, deprivation, social exclusion and ill-health. Socioeconomic disadvantage in childhood, inadequate nutrition, poor education, unemployment, and psychosocial factors (such as lack of self-esteem and social support, often associated with addictive behaviours) are causative of ill-health, and this can occur with or without access to good-quality medical care.1-3 Recognition of Indigenous people's prior ownership of the land is central to their achieving social and economic equity in Australia A child raised in an affluent home is likely to succeed educationally, which in turn favours entry to more privileged sectors of the labour market, with financial security in old age. A child from a disadvantaged home is likely to achieve few educational qualifications, leave school at the minimum age, and enter the unskilled labour market, where pay is low, the work often hazardous, and old age means reliance on the welfare system. A number of longitudinal studies confirm these relationships and show that they result in higher morbidity and mortality for the more socially disadvantaged.1,2 There are biologically plausible links between social and economic disadvantage and health. If the biological stress response is activated too often and for too long, there are multiple health effects -- depression, increased susceptibility to infection, glucose intolerance leading to diabetes, and high blood pressure and accumulation of cholesterol in blood vessel walls leading to heart attack and stroke. A life-course perspective views a person's physiological status as a marker of their past social position. Thus, past social experiences become written into the body's physiology and pathology.1-3 The situation for Indigenous Australians is further exacerbated by racism and prejudice, which have marginalised them from various aspects of social and community life, with additional detrimental effects on health. What evidence is there that this relationship between health and social disadvantage has adversely affected Australia's Indigenous people? Life expectancy at birth, which is an overall measure of health status, is 56.9 years for Indigenous men and 61.7 years for Indigenous women, compared with 75.2 years and 81.1 years, respectively, for non-Indigenous men and women.4 In 1997, fewer than 31% of Indigenous students remained in Year 12, compared with over 72% of non-Indigenous students. In the 1996 Census, while Indigenous people made up only 2.1% of the Australian population, they accounted for 19% of the adult prison population,4,5 and 41% of the inmates of juvenile corrective institutions4 (and the proportion of young Indigenous people in detention has increased further since the introduction of the mandatory detention laws in Western Australia and the Northern Territory5). The unemployment rate for all Indigenous Australians is likely to increase from 39% to 47% by the year 2006.6 Indigenous households are more likely to be overcrowded, but, despite this, have a lower median weekly income. Similarly, other measures of social disadvantage also show an over-representation of Indigenous people. Understanding the social determinants of health and these disturbing figures and taking the Indigenous health debate to the next level has always been fraught with misconceptions. A common myth concerns the high levels of spending on Indigenous health, and this has been debunked in a recent report showing that, for all health services, recurrent expenditure on a per-person basis was only 8% higher for Indigenous compared with non-Indigenous people. Furthermore, Indigenous people benefit very little from Medicare and the Pharmaceutical Benefits Scheme, with drawing rates only 27% and 22%, respectively, of non-Indigenous levels.7 Another major myth is that Indigenous people do not want to help themselves. It is true that you cannot help people unless they want to help themselves, but, in relation to education, numerous reviews, inquiries and consultations in recent years have reported that, contrary to popular belief, Indigenous people do place a high priority on education: "They want for themselves and their children no less than is afforded other Australians. They expect that educational processes should lead them to acquire the knowledge and skills necessary to realise their individual potential, lead satisfying lives, and contribute actively to the community."6 The current approach to Indigenous health is exemplified by the Western Australian Indigenous Child Health Survey. This is a population survey of an estimated 3150 children, aged from 0 to 17 years, which aims to improve our understanding of the health and educational needs of Indigenous children. The results will be used to develop a planned approach to the desired improvements in this area. For example, the initial WA Child Health Survey resulted in an improved range of State and national programs. These programs placed an emphasis on early intervention and prevention in child and adolescent mental health services, parenting strategies and programs, school programs for students at educational risk and promotion of mental health in schools. These data are also required for Australia to meet its obligations to the United Nations to report on the health status of Indigenous children. At a national level one of the most significant recent developments has been the establishment of the Office for Aboriginal and Torres Strait Islander Health Services in the Commonwealth Department of Health. Since it was established in 1995, there has been a more comprehensive planning and funding strategy targeting Indigenous health issues, with improved focus on primary healthcare and Aboriginal community involvement in healthcare delivery. While these efforts in health and education are encouraging, they do not address the prevailing attitudes in Australian society which marginalise and disempower Indigenous people. T S Eliot wrote: "We shall not cease from exploration And the end of all our exploring Will be to arrive where we started And know the place for the first time."8 Since arriving in Australia, the non-Indigenous population have wanted to believe that this was a "Terra Nullius", an uninhabited land that they could possess and use to their advantage without recognising the rights of the Indigenous peoples.9 Non-Indigenous Australians might gain a better understanding of Australia when they fully appreciate the inherent truth in Indigenous people's claims to land, justice and livelihood in this nation. Recognition of Indigenous people's prior ownership of the land is central to their achieving social and economic equity in Australia. In March 1999 the United Nations Committee on the Elimination of Racial Discrimination found that the Federal Government's 1998 amendments to the Native Title Act 1993 are in breach of Australia's obligations under the Convention on the Elimination of All Forms of Racial Discrimination. It is argued that these amendments fail to respect the cultural identity of Indigenous people and fail to promote the preservation of their culture, as required by the United Nations.10 The Council for Aboriginal Reconciliation continues working to achieve its vision of "A united Australia which respects this land of ours; values the Aboriginal and Torres Strait Islander heritage; and provides justice and equity for all."11 The cause of reconciliation has been furthered in recent years by improved spending on health services and health programs, particularly by the Commonwealth Government. These efforts need to continue and to become more appropriate and focused. The major challenges of the future centre on the reconciliation process, and the willingness of all Australians to take the actions that bring symbolic and material change. Facing these challenges with integrity and courage will benefit Australia's Indigenous people and the nation as a whole. Sandra J Eades Indigenous Health Research Unit, Population Sciences Division TVW Telethon Institute for Child Health Research Derbarl Yerrigan Health Service; and Department of Paediatrics University of Western Australia, Perth, WA sandyATichr.uwa.edu.au Marmot M, Wilkinson RG, editors. Social determinants of health. New York: Oxford University Press, 1999. Keating DP, Hertzman C, editors. Developmental health and the wealth of nations: social, biological and educational dynamics. New York: The Guildford Press, 1999: 25-35. The relationship between fetal malnutrition and chronic diseases in later life [editorial]. BMJ 1997; 315: 825-826. Australian Bureau of Statistics. Health and welfare of Australia's Aboriginal and Torres Strait Islander peoples. Canberra: ABS, 1999. (Catalogue No. 4704.0.) Human Rights and Equal Opportunity Commission. Mandatory detention laws in Australia. <http://www.hreoc.gov.au/human_rights/child_rights/h5_1_7.htm> (Accessed 19 April 2000). Commonwealth Department of Education, Training and Youth Affairs. Indigenous school to work transitions, 1998. <http://www.detya.gov.au/publications/schooltowork/default.htm> (Accessed 19 April 2000). Commonwealth Department of Health and Family Services. Expenditure on Health Services for Aboriginal and Torres Strait Islander People. Canberra: DHFS, 1998. Four Quartets: Little Gidding: V, lines 26-29. The complete poems and plays of TS Eliot. London: Faber & Faber, 1969: 197. Reynolds H. Why weren't we told? A personal search for the truth about our history. Ringwood: Penguin books, 1999. Human Rights and Equal Opportunity Commission. Submission to the United Nations Committee on the Elimination of Racial Discrimination: Response to the request for information in relation to Decision 1(53) concerning Australia 1998. <http://www.hreoc.gov.au/social_justice/native_title/index.html> (Accessed 19 April 2000). Council for Aboriginal Reconciliation. <http://www.austlii.edu.au/au/orgs/ car/index.htm> (Accessed 19 April 2000). Make a comment

Sandra J Eades

Editorial William Osler: a model for the 21st century? Osler's teachings are as relevant now as they were 100 years ago Whatever way my days decline, I felt and feel, tho' left alone, His being working in mine own, The footsteps of his life in mine. MJA 1999; 171: 577-579

Michael F O'Rourke

History The suicide of Thomas Wentworth Wills Thomas Wentworth Wills was the most important Australian sportsman of his time. He captained the Victorian colony at cricket and was the first hero of Australian Rules football. Although his picture now adorns the conservative Melbourne Cricket Club, he died in 1880, an isolated, destitute alcoholic, after stabbing himself in the heart. Wills embodied a tradition, as prevalent today as it was over 100 years ago, that weds sport with alcohol in Australian culture. Gregory M de Moore MJA 1999; 171: 656-658 Introduction - Alcohol abuse, delirium tremens and suicide - Acknowledgements - References - Authors' details - - More articles on History Illustration: an 1870 oil painting of Thomas Wills.

True Story A riposte for a fencer The residency appointment of Alfred Edmund Finckh to Sydney Hospital in 1905. Was it just a matter of male chauvinism? Alfred Finckh gained a residency at Sydney Hospital in 1905 in preference to a more academically successful female medical graduate, amid some controversy over the place of female doctors in hospitals. Here, two of his descendants argue his cause: that he was an experienced scientist with qualities that merited his selection for the post. MJA 1999; 171: 679-680

Ernest S Finckh · Andrew S Finckh

Rescue Medical response to disasters Doctoring at its best MJA 1998; 169: 601 Disasters are predictable, not in time or place, but in their inevitability. In the South Pacific region there is an ever-present threat of cyclones, floods, fires, earthquakes and volcanic activity. Australian health teams, both defence force and civilian, have played major roles in the Brisbane floods (1974), Cyclone Tracey (Darwin, 1975), the Ash Wednesday bushfires (1983), the Newcastle earthquake (1989), and the Katherine floods (1997), to name but a few. Emergency offshore deployments involving military medical services have brought rescue and relief to victims of the Mt Lamington disaster in Papua New Guinea (1951), to Rwanda in the aftermath of the civil war (1994-1995), to the drought and famine devastation in Irian Jaya (1998), and in recent months to the Aitape tsunami disaster in Papua New Guinea. RAAF health, rescue and reconstruction teams are deployed regularly to the Solomon Islands and other South Pacific nations after cyclone disasters. By their nature, disasters disrupt the normal functioning of society, and extra and specialised training and skills are needed to equip doctors, nurses and other health professionals to operate in a devastated environment. Adrenalin surges are high, and the response team members must constantly face personal and collective risks. Relations at the interface between the defence force and civilians may become strained, and there are always political issues of cost, job demarcation and international liaison, and sometimes (as in Rwanda) armed conflict, which impinge on doctors involved in disaster response. After prior training and rehearsal of training systems, being a doctor in a disaster response team can be an experience of the greatest professional fulfilment. There is no better example of this than the health response to the 1998 Aitape tsunami disaster. What lessons have re-emerged from that deployment? A disaster implies numbers of sick and injured that overwhelm the resources available for rescue and treatment. However, irrespective of the scale of a disaster, it is individuals who are dead, trapped or injured, and from each individual's point of view treatment is needed irrespective of whether or not there are a hundred or a thousand others in a similar plight. But the collectivity of individual victims of necessity changes the approach of the medical teams involved in disaster response. The skills (and heartbreak) of triage, the need for speed (the greatest good for the greatest number), and the importance of prevention of secondary trauma and disease are core themes in the repertoire of health teams responding to disaster. The articles in this issue of the Journal by Taylor et al and Holian and Keith illustrate well the importance of these themes. One of the greatest resources for individuals and societies afflicted by disaster is the preservation of family units. By Day 8 following the Aitape tsunami disaster, all surviving orphan children were being cared for by relatives of their extended families; and surviving parents who had lost all their children had, in some cases, adopted the children who had been recently orphaned. Before the arrival of medical teams, the application of simple first aid skills may often save lives and prevent serious complications of injury and disease. In the Aitape tsunami disaster many victims with fractures, impalements and lacerations had not had simple self-applied or buddy-applied first aid, with the inevitable consequences of unstabilised fractures, cellulitis, and gangrene and septicaemia of the wounds. Currently, 1 in 30 Australians are trained in first aid; this becomes a priceless resource when disasters strike. All military personnel are trained in the skills of first aid, but many civilian workers in non-government organisations are deployed without these basic skills. In the Rwandan emergency less than 20% of the civilian field workers possessed a current first aid certificate. The most effective way in which Australian doctors can help in future disasters is by joining one of the three Services (as reservists) or one of the non-government organisations (such as the Red Cross or St John Ambulance, Australia). As part of a trained, properly equipped team they can then offer the necessary personal skills for emergency deployment. In the 1998 Aitape tsunami disaster, health reservists from the Royal Australian Navy, the Australian Army, and the Royal Australian Air Force served as essential members of the regular military teams. To these teams were added the Monash Medical Centre Surgical Team and health professionals of the defence forces of New Zealand and the United States. Such is doctoring at its best. Major General John Pearn, AM, RDF The Surgeon General, Australian Defence Force c/- The Royal Children's Hospital, Brisbane, QLD Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Rescue Operation Shaddock -- the Australian Defence Force response to the tsunami disaster in Papua New Guinea Operation Shaddock was the name given to the deployment of a major field medical unit of 58 Australian Defence Force medical and other personnel to Vanimo, in northwestern Papua New Guinea. Hundreds of victims of the tsunami disaster were treated and more than 200 surgical procedures performed in a 10-day mission. Paul R P Taylor, David L Emonson and James E Schlimmer MJA 1998; 169: 602-606 Introduction - A command perspective - A clinical perspective - Conclusions - Authors' details - - More articles on Emergency medicine Introduction When the extent of the devastation caused by the Aitape tsunami (Box 1) was realised, over 12 hours after the wave hit, a request from the Government of Papua New Guinea (PNG) for air transport support and a field hospital was sent to the Australian Government aid agency AusAid. The request was passed to Emergency Management Australia(the link organisation between military and civilian agencies), which in turn asked the Australian Defence Force (ADF) to respond. By 1900 on Saturday 18 July, the requirements were more clearly defined as: Surgical teams; Nursing teams (for low and medium dependence patients); Primary healthcare teams; An aeromedical evacuation capability; and Preventive medicine (public health) support. Personnel from the 1st Parachute Surgical Team, the 1st Field Hospital and an Aeromedical Evacuation (AME) team from No. 3 RAAF Hospital (all Sydney units, based at Holsworthy and Richmond) worked through the night of 18 September to prepare essential equipment. Early on the evening of Sunday 19 July two RAAF C-130 transport aircraft carrying the health facility left Richmond RAAF base and landed at dawn the next day at Vanimo, a town some 70 km to the west of the disaster area. By nightfall the initial team of 25 ADF health personnel (six doctors, six nurses, two operating theatre technicians, 10 medical assistants and a preventive medicine officer), supported by logistics, movements and communications staff, had erected a field health facility around an abandoned PNG military barracks about 1 km from Vanimo hospital. The threat of further seismological events was very real and an evacuation plan was put in place in the event of a subsequent tsunami. The team worked around the clock for the next four days, stopping only briefly to grab a snack from field ration packs. Around the periphery of the area devastated by the 33 km wide tsunami, houses like the one above were badly damaged; in the central area nothing was left standing. The ADF team at Vanimo was later reinforced by an orthopaedic surgical team (three surgeons, one physiotherapist, one operating theatre nurse and a cast technician) from Monash Medical Centre in Melbourne (see Holian & Keith), an additional ADF orthopaedic surgical team (surgeon and anaesthetist from Sydney), a health team from the New Zealand Defence Force (NZDF) and one from the US military (one surgeon, two preventive medicine officers). An ADF health team consisting of a medical officer, a nursing officer, a health logistician and two health administration officers, who were in Port Moresby to assist in the review of the PNG Defence Force Health Services, were also made available to support the mission. In total, 251 patients were treated at the ADF health facility during Operation Shaddock and 209 surgical procedures were completed. Hundreds more patients were seen and treated by the teams in the disaster area and the care centres. Only two deaths occurred in the facility, both non-surgical cases involving aspiration pneumonitis from near-drowning. While the surgeons operated, primary health care and public health teams worked with engineers and aircrew to prevent the outbreak of disease. ADF personnel were involved in ensuring that drinking water was potable, waste (including sewage) was disposed of, and the dead were buried. RAAF aircrew worked to transport food, water, and counterdisaster equipment, and to evacuate the victims of the disaster. In all, nearly 200 ADF personnel contributed to Operation Shaddock. A command perspective The immediate challenge to the Parachute Surgical Team and other units was how to plan for a disaster in which, potentially, the scale of destruction and the numbers of injured were enormous, but for which exact details were unknown. We also had to tailor our units, designed to treat war wounds of fit young men, to care for the young and the old with all types of injuries and concurrent medical illnesses. 1: The Aitape tsunami disaster, Papua New Guinea, July 1998 A series of three tsunamis struck the north Papua New Guinea coast, west of the village of Aitape, at about 1930 (local time) on Friday 17 July 1998. The local population had virtually no warning of the approaching waves, variously reported as 7, 10 and 15 m in height, which travelled across the surface of the Pacific Ocean at speeds in excess of 100 km/h and struck the coast across a 33-km front. News of the disaster and the plight of the people first became known when a Catholic Church mission began its daily radio broadcast to its outstations the following morning. By mid morning of Saturday 18 July, reports received in Port Moresby revealed the magnitude of the disaster. As a result of the tsunamis at least 16 villages were destroyed, causing more than 2200 deaths, displacing about 9000 people and devastating an area of 40 km2. More than 700 people were hospitalised in the various medical facilities in the area. All that Saturday night (18 July) we worked to deploy in 14 hours an organisation which notionally requires seven days' notice. Personnel were recalled to duty and worked around the clock to pack equipment and procure items from stores. The next morning was spent reconciling orders and deliveries, further packing, and in briefings and administration. By mid-morning on Sunday 19 July the trucks and buses arrived to take us to RAAF Richmond. Even before we left we were weary. The first flight left at last light, arriving in Port Moresby at 0300 Monday morning (20 July). After quickly refuelling and changing crew, we took off for Vanimo, arriving just as dawn broke. It was now 52 hours after the first tsunami had struck. We arrived amid preparations for the third day of the evacuation of people from the disaster area. Every available light aircraft and helicopter was being prepared for non-stop operations in the daylight hours in an attempt to complete the evacuation. Brother James Coucher, the missionary who had been coordinating the relief effort so far, was at the airport, exhausted but obviously relieved and happy to see us. In a desperate bid to maximise the evacuation airlift back to Vanimo, casualties had been brought in piled on top of one another, with injured limbs lying at odd angles. Placing the injured in splints and on stretchers would have greatly reduced the numbers able to be evacuated. Pilots described having to perform triage themselves in making decisions about who to leave behind. Teams consisting of a doctor, an interpreter and a medical assistant were immediately sent into the disaster area in order to collect information on the situation. The evacuees and those still awaiting evacuation appeared bewildered. The scale of the disaster was simply incomprehensible to them. Entire communities had been washed away in a moment. Everyone had lost at least one relative; many had lost all. Many survivors were wandering around the lagoon desperately trying to find a relative, dead or alive. The evacuation was in its last stages. The issues now needing attention were those of displaced people, disposal of the dead, and the definitive treatment of patients already evacuated. Our first action, while setting up the facility, was to visit each of the care centres and the hospital in Vanimo. Vanimo Hospital did not have surgical staff, so several patients required immediate surgery. Nine major surgical procedures were undertaken at Vanimo before the field hospital was set up. Other patients requiring surgery were found in the care centres. The response by the local population in Vanimo was overwhelming. Within minutes of our arrival, a fleet of vehicles was at our disposal, and pledges given for all the assistance we could ask for. Local church communities guaranteed that all of the patients would be fed and looked after, and that orphans would have someone by their bed. Our field hospital consisted of a triage/resuscitation area, an operating theatre with equipment to run two operating tables, a self-contained ward facility with 20 beds, supported by x-ray, pathology (we could perform most routine tests and cross-match blood), and a preventive medicine laboratory. Initially, we ran two operating tables and a third for minor wound debridement. Our staff comprised a consultant surgeon, an orthopaedic registrar, a consultant anaesthetist and three general duties medical officers. 2: Surgical load and new patients admitted to the ADF facility, Days 1-9. Just as we were completing the first phase of setting up the field hospital, the evacuation aircraft began to return, and on the first day alone 124 patients were delivered to our facility. Thirty-nine surgical procedures were performed that day (Box 2, above), and by day's end we had 76 patients in a 20-bed facility. Extra wards were "commissioned" in the surrounding barracks using our soldiers' camp beds. Low- dependence patients were transferred to care centres in local schools and community centres. One of the eight-bed field wards of the ADF facility. The pace was similarly hectic on the second and third days; however, by the end of the fourth day, as most of the primary surgery has been completed, the pace began to slow. Then a phone call from Aitape reported that a patient had developed gas gangrene. A light aircraft and a pilot were found within an hour of last light and dispatched to retrieve this patient as well as some with less serious conditions. The aircraft returned with 13 patients, all requiring surgery that night! During the second week tactical aeromedical evacuation of patients was undertaken to spread the surgical workload between the hospitals at Vanimo, Wewak and Aitape. This also enabled us, working with the Monash Orthopaedic Surgical Team, to move nearly 40 patients (and relatives) to Wewak Hospital, where the operating and recovery facilities were more suited to patients needing orthopaedic surgery. After the fifth day the majority of surgery undertaken involved delayed primary closure of wounds, with or without skin grafting. The wider problems were now largely those of coordination and appropriate management of the care centres for displaced people and the attendant public health implications. Significant effort was needed to channel the international donations of staff and supplies to areas of need. Coordination of resources is the key to any disaster relief situation. In time, the organisation and response became increasingly efficient. The care centres were well set up inland, and various teams, both military and civilian, were providing basic medical care, well organised shelter and food. By 10 days after arrival, the workload was declining (Box 2). Each patient's wounds had been debrided, and many wounds were now closed or grafts had been performed. Although surgical procedures were performed right up to the last day of the deployment, we concentrated our efforts in the last few days on discharging patients from the ADF facility and arranging their ongoing care within local health facilities. When our remaining postoperative patients had been transferred we stopped operating, with only three out of 209 surgical patients still requiring wound closure. A clinical perspective As we arrived in Vanimo 52 hours after the tsunami, we had missed the first two peaks in deaths from trauma (Box 3), but had arrived in time to prevent the third peak, which occurs several days or weeks after injury. Indeed, the ADF contingent treated no patients with intracranial, intrathoracic, abdominal or spinal injuries as these patients had already succumbed before our deployment. Furthermore, few infants and elderly people had survived. 3: Trimordial distribution of deaths from traumatic injuryFirst peak -- seconds to minutes Injury incompatible with life (eg, aortic dissection). Second peak -- minutes to hours Focus injuries of early management of severe trauma (eg, haemorrhage, haemopneumothorax). Third peak -- days to weeks Complications, sepsis, multiorgan failure. Every patient treated on the first day had some degree of aspiration pneumonitis from near-drowning. Two patients were admitted in respiratory failure and treated with antibiotics, nebulisers and oxygen, but had little chance of survival. Many also had underlying respiratory disease; tuberculosis is endemic in the local communities. Anaemia was also common, usually owing to malaria or intestinal parasite infestation. All these problems complicated the patients' anaesthetic and surgical management. There were many large flap scalp lacerations caused by floating debris, and many fractures and dislocations, both open and closed. At least a quarter of all patients were children, many with simple soft-tissue injuries and lacerations. Another patient is moved to the recovery area after operation. Many patients required immediate surgery, but those triaged into the delayed-treatment group were rapidly deteriorating. All wounds were grossly septic and contaminated with foreign material such as sand, coral and vegetation and, as such, were at least limb if not life threatening. Many victims had been impaled upon the mangroves behind the Sissano lagoon by the force of the waves. The complete destruction of village aid posts and their workers resulted in virtually no medical attention being available to casualties initially. Dehydration compounded blood loss and worsening cardiovascular shock. Patients with large bone fractures were often transported unsplinted, and some developed presumed fat embolism syndrome, further worsening their preoperative condition. Surgery All patients brought to the ADF facility were initially rapidly triaged, with assessment and resuscitation proceeding simultaneously. All casualties were treated according to Australian Defence Force casualty treatment regimens -- a system of simple, reliable, reproducible treatment protocols based on accepted practice. Surgical procedures were based on principles espoused by the Red Cross (Box 4), which has by far the most extensive current experience of dealing with large numbers of casualties in situations with limited resources. 4: Red Cross surgical principlesWound assessmentWound excision and "decompression"Antibiotics (intravenous chloramphenicol)Undisturbed dressing techniquesOdour, temperature and pulse as indicators of inadequacy of initial wound surgeryDelayed primary closure with or without skin grafting at 4-5 days All wounds were extensively debrided and devitalised tissue removed. An aggressive approach was often required, and 14 amputations were performed. Fractures were aligned and immobilised with plaster slabs and improvised splints. Open fractures were debrided and thoroughly lavaged with sterile saline and immobilised with combinations of plaster and skeletal traction. Femoral fractures were managed initially with skeletal traction using Steinman pins and the patients were then flown to Wewak for definitive treatment by the Monash orthopaedic surgical team. Surgery was performed in two stages -- initial wound surgery, and then delayed primary closure. All surgical wounds were left open, using ample absorbent gauze dressings. Chloramphenicol and metronidazole, used in local practice and hence readily available, were used for antibiotic cover. Delayed primary closure was carried out four to five days later, as were the first split skin grafts. All split skin grafts were successful, at least until the time of our departure! Six wounds required further debridement. The parameters of odour, temperature and pulse rate were effective in identifying patients in whom initial debridement had been inadequate. Anaesthesia With such great demands on our meagre resources, there was a need to adopt a "standardised" approach to anaesthesia while still tailoring techniques to individual patients. As a result, recovery staff and medical assistants with little or no experience knew what to expect and how to manage patients postoperatively. Airway management, monitoring, induction and maintenance of anaesthesia often had to be performed before complete volume expansion had been achieved. Despite good interpreters, a complete medical history was frequently lacking and we thus had to be ever- vigilant for occult injuries and problems. We would often be overseeing three or sometimes four or five patients under general anaesthesia, with assistance from the ADF general medical officers. Anaesthesia was kept simple and safe and, where possible, the selection of anaesthetic agents was individualised. No premedications were used. For induction, ketamine was preferred, although thiopentone and propofol (Diprivan; ICI) were also used. Ketamine, which does not induce hypotension on induction and stimulates ventilation, was most suitable in these circumstances. In some cases, rapid-sequence induction and intubation using suxamethonium was used. Laryngeal mask airways were extensively used, as spontaneous breathing was the order of the day. This was safe, made monitoring simpler, used resources (one ventilator) more effectively and allowed a greater margin of error -- we were all exhausted. We used oxygen concentrators for oxygen supply. These are solid little machines producing 3-4 L/min of 90%-95% oxygen. We did not take nitrous oxide, which was considered dangerous cargo by the RAAF. Maintenance of anaesthesia was achieved with either ketamine, halothane or isoflurane. Narcotics were given intraoperatively; fentanyl, preferred because of its short half-life and high potency, was given intravenously. A standard combination of crystalloid and colloid (Hartmann's solution and Haemaccel) was used for intravenous volume replacement. Transfusions (a maximum of two units per patient, as supply was limited) were given when indicated; blood was obtained initially from Sydney and later from Port Moresby. Non-invasive methods of intraoperative monitoring were used. At times monitoring equipment was in short supply. Blood pressure, electrocardiograms, pulse oximetry and capnography provided basic information and proved reliable. Very little local or regional anaesthesia was used. Brachial plexus blocks were successful; however, spinal or epidural blocks were generally contraindicated because of coexisting sepsis. Postoperative requirements for opiates were minimal. The patients were uncomplaining; in some instances they had to be forced to accept pain relief. The atmosphere on the wards was sombre. The enormity of the disaster was simply too great to comprehend in those first few days. All of our patients looked shell-shocked, simply lying still, and taking little food. Conclusions In all, 124 primary surgical procedures and 85 secondary procedures were performed at the ADF health facility in Vanimo in the space of 10 days. In addition, about 25 other patients were operated on by ADF personnel at both Vanimo and Wewak hospitals. The success of our mission, in both humanitarian and international terms, lay in the ADF team approach -- fast, efficient and effective management of the casualties, and utilisation of all available personnel and resources for the best possible patient care. Medical officers, nursing officers and medical assistants, both regulars and reservists, all worked tirelessly to achieve this common goal. When we completed our mission each of the hospitals and care centres in the area had the staff, experience, stores and pharmaceuticals needed to continue its work. Displaced persons camps were well established, with shelter, clean water, food, health support and appropriate preventive health measures in place. Vaccination programs were planned, and resources and staffing needs identified. We were satisfied that we were leaving with all of the infrastructure in place to cope with the needs of the people, now and for the foreseeable future. Many of the soldiers deployed knew well the stories of how, during the second world war, the PNG people, who became known as the "fuzzy wuzzy angels", had helped wounded Australian soldiers back to aid posts. We considered our mission as simply "returning an old favour". A very moving farewell "sing sing" was testimony to the difference that our efforts had made and of the special relationship that exists between Australia and Papua New Guinea. Authors' details Holsworthy MILPO, Sydney, NSW. Paul R P Taylor, MB ChB, FRCS(Edin), Major, Officer Commanding, 1st Parachute Surgical Team, Coral Lines. James E Schlimmer, MB BCh, MMed(Anaes), Major; Medical Officer and Anaesthetist, 1st Field Hospital, Manunda Lines. Defence Health Service Branch, Canberra, ACT. David L Emonson, MB BS, Group Captain, Director of Health Planning and Intelligence. Reprints will not be available from the authors. Correspondence: Group Captain D L Emonson, Director of Health Planning and Intelligence, Defence Health Service Branch, Campbell Park Offices, Canberra, ACT 2600. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

David L Emonson · James E Schlimmer

True Stories Breaching the bastions. Susannah O'Reilly -- pioneer Australian female doctor An honours graduate in medicine from the University of Sydney in 1905, Susie O'Reilly was rejected by Sydney Hospital's male-dominated medical establishment, amid much controversy in the local press. She went on to become a popular family doctor and obstetrician, and was one of the founders of the Rachel Forster Hospital for Women. MJA 1998; 169: 648-650 Ever-cheerful, with a limerick for every situation and occasion, Susie O'Reilly was a popular family doctor and obstetrician on Sydney's North Shore for much of the first half of this century. Caring little for conventional fashions, Susie made her many calls wearing, in addition to her usual broad smile, a hygienically laundered voluminous white dress or uniform (shapeless and waistless) with a black hat perched on top of her frizzy hair. But, in addition to her sparkling personality1 and appearance, Dr Susannah Hennessy O'Reilly (1881-1960) was also remarkable historically, as one of the pioneer women in medicine in Australia. In common with many true pioneers, Susie experienced at least one major set-back in her career. She was refused a residency at Sydney Hospital in 1905, despite much in her favour -- excellent academic standing, impressive family connections, and an earlier claim made by the then Board of Directors that "there is nothing in the rules and regulations to prevent women doctors from being appointed".2Susannah O'Reilly was born on 25 January 1881 in Liverpool Street, Sydney, the eldest daughter of Dr Walter William Joseph O'Reilly. Her father, born in New York and educated at Sydney's Newington College, had obtained his medical degree at Queen's University, Belfast. His father, Walter Le Croix O'Reilly, and his grandfather Bernard O'Reilly, were also medical men, both graduates of Trinity College, Dublin. Susie O'Reilly aged 12 years Susie was admitted to Methodist Ladies' College (then known as Burwood Ladies' College) on 18 July 1894, as a weekly boarder. A remark in the Admissions Book -- "studiously inclined" -- aptly sums up one aspect of her nature. As for another, it is reported that one night after "lights out" she was caught swinging from the bracket of one of the gas lamps in the dormitory.3 She was Dux of the School in 1897 and passed the Senior in 1898, matriculating with first class honours in French. Proceeding to Sydney University, Susie passed first year medicine in 1899 and, majoring in biology, also gained a BSc (with her medical subjects counting towards it), conferred in 1903. She was one of the top four students for each of the last three years of her medical studies, graduating MB early in January 1905 with second-class honours. The newly graduated Dr O'Reilly applied for the position of Resident Medical Officer at Sydney Hospital in 1905. She learnt of her unsuccessful application when she received a letter from the Registrar of the University of Sydney stating that at a joint meeting of the representatives of Sydney Hospital and the Royal Prince Alfred Hospital, held on 3 January 1905, five gentlemen -- F G W Simpson, J W Power, S Kay, E A R Bligh and A Verge -- had been selected as Resident Medical Officers for Sydney Hospital for that year. Simpson and Power had come first and second, respectively, in their graduating years' order-of-merit list; the latter three had received passes in the examination results.4 The Registrar had then asked the Board to choose between A E Finckh and Susie O'Reilly for the sixth place. Finckh obtained eight votes to Susie's seven. Of the five doctors on the Board, two voted for Finckh, two for Susie, and the fifth, the Board President (Sir Arthur Renwick), abstained.5 The Board's decision to choose Finckh over Susie was remarkable for many reasons, not the least being Susie's superior academic record. The Board had previously informed Annie Golding, President of the Women's Progressive Association of New South Wales, on 21 July 1903,2 that "when it is necessary to make appointments to the medical staff, applications are invited through the press, with no restrictions as to sex". Further, one of the Board members who voted against Susie's appointment, Dr Joseph Foreman, Honorary Gynaecologist at Royal Prince Alfred Hospital, and Lecturer in the Diseases of Women in the Faculty of Medicine, University of Sydney, gave her an excellent reference, written on 20 January 1905, less than three weeks after the ignominious Board vote (Mike O'Reilly, biographer, Sydney, personal communication). To quote: "I have much pleasure in stating that Miss O'Reilly was one of my clerks for three months. She was very keen in acquiring knowledge, and also successful as appears in her position in the pass list. I have a very high opinion of her ability and can recommend her in every way." Moreover, and perhaps most surprisingly of all in its apparent lack of influence, was the fact that Susie's father, Walter, was a member of the consulting staff at Sydney Hospital from 1888, and had previously been an honorary physician there. So, why was a man with a pass degree chosen ahead of a woman who came fourth in her year, and who possessed an honours degree? Turning to the press of the day, we are left with the strong impression that there was little more to it than gender bias, evident in Sydney more so than elsewhere in Australia at the time, with Susie and her sorority perceived as trying to prise their way into a heavily fortified male-dominated preserve. The Establishment newspaper, the Sydney Morning Herald, promptly and simply reported the Board meeting on 4 January 1905, but the Daily Telegraph lent Susie's plight editorial support the following day: "In the view of the directors her sex was a fatal disqualification. They [the directors] did not hesitate to put the matter plainly on that ground, and lay down the principle that no female shall hold the position of resident doctor at the Sydney Hospital", and concluded "The girl who braves the vulgar prejudice which seeks to prevent women from entering a profession where humanity calls so loudly for their presence deserves the support and encouragement of all enlightened people. Yet Sydney has the distinction of having men in highly responsible positions who, on principle, feel it is their duty to increase the difficulties against which the female student of medicine has to contend."6 Letters to the Editor of the Daily Telegraph followed swiftly. Dr Mary Booth wrote that the question of hospital appointments had been a bitter one among women in Sydney for many years: they had been obliged to go to Adelaide and Brisbane for experience.7 A letter from "Patient" opined that this was as it should be.8 The writer endorsed Dr Booth's opinion that there was room for both men and women doctors, "but without injury to the efficient working of the hospitals, and therefore to the patients, there is no room for women on the resident medical staffs of the Sydney and Prince Alfred Hospitals. It is unquestionably right and proper that women should have opportunities for gaining practical experience, but surely the Children's Hospital, and the four or five women's hospitals of Sydney should be amply sufficient for this purpose. Why should they wish to acquire a knowledge of men's diseases, which they will never be called upon to treat in private practice, is incomprehensible to the ordinary mind . . . I suggest, in all sincerity, that steps be taken by these dissatisfied ladies, to establish a hospital for women, managed, officered, and run entirely by women".8 A short time later, in March 1905, a three-part series on the general subject of "Sydney's Medical Women", by "AHK", ran in the Evening News, reporting further views on the matter. AHK quoted a woman doctor who did not deny that women had equality in their training at Sydney University, but that this stopped as soon as they graduated and began competing with men in the market-place for jobs and training.9 She compared Sydney very unfavourably with London. AHK also quoted a male doctor, who advanced economic reasons for the prejudice in Sydney against women in medicine: the women had come into the field at a bad time, he claimed; 1903 was the year of the financial crashes and when the land-boom had burst. Since then, things had been "horribly bad", and "the faculty" were perhaps the greatest sufferers in times of financial hardship. It had been no academic protest against women's invasion of man's sphere, but "a veritable war to the knife . . . the outcome of the bitter struggles for existence of the last twelve years". Hostilities had been more or less veiled of late, but nothing like a truce would be called until economic prospects improved. There was little likelihood of doing so at present. While many in the profession had to live chiefly by "anaesthetic fees", one could scarcely expect them to look upon the encroaching sex with equanimity. AHK went on to say that this doctor's gloomy summary was borne out by the number of houses lately vacated by professional men. In the last week there were six empty "doctor's houses" in Hyde Park, a thing unprecedented in his informant's memory. ("Starved out," he commented.) When men were fighting for bare life themselves, added the doctor, they did not feel disposed to help any poachers on their domain.10 Many years later, in the Sydney Morning Herald's obituary for Susie, Sir Herbert Schlink eloquently understated the problem: "The men doctors did not take too kindly to women in medicine at first."11 In fact, in 1906, women began to make their way in the hospitals of Sydney, claimed at the time to be the the most conservative of Australian cities.8 While women were not appointed to Sydney Hospital until 1910, Royal Prince Alfred Hospital was "breached" in 1906 with the appointment of Dr Jessie Aspinall. Luckily for Susie, female doctors were not excluded from public hospital appointments in all Australian cities, and she undertook her internship at Royal Adelaide Hospital in 1906-1907, returning to Sydney in 1908 and eventually becoming one of the foundation members of the Rachel Forster Hospital for Women in 1922. Three of Susie's family also graduated in Medicine from Sydney University: a brother, Linnell (1879-1948), appointed to Sydney Hospital in 1906, a year after Susie's rejection; another brother, Merrick (1892-1957), appointed to Perth General Hospital in 1914; and a sister, Olive (1892-1976), to Brisbane General Hospital in 1916. Today, nearly a century later, women in professions continue to come up against similar bastions of authority and power -- in the Church and the Navy, for example. Nor is the opposition confined only to men. Kelvin Grose, BA (Hons), PhD PO Box 197, Killara, NSW 2071 Obituary. Susannah Hennessy O'Reilly. Med J Aust 1960; 2: 516-517. Golding A. Letter to the editor. The Daily Telegraph (Sydney)1905 Jan 6. O'Reilly M. The O'Reilly family. In: Halstead G. The story of St Ives. Sydney: Nungurner Press, 1982: 344. University of Sydney Calendar for 1905, p 286. Minutes of Meeting of the Board of Directors, Sydney Hospital, held on 3 January 1905. Sydney Hospital Archives, pp 414-415. The Daily Telegraph (Sydney) 1905 Jan 5. Booth M. Letter to the editor. The Daily Telegraph 1905 Jan 7. The Daily Telegraph (Sydney), 1905 Jan12. "AHK". Sydney's medical women. The Evening News (Sydney) 1905 Mar 31; p 7 (column 5). This is the third of three articles, beginning on 28 March 1905. The Evening News (Sydney) 1905 Mar 29; p 6. Obituary. Susannah Hennessy O'Reilly. Sydney Morning Herald 1960 Jun 22. Margaret Coleman. This is Pymble College. Pymble Ladies' College, Sydney, 1991; p 53, p 119. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Kelvin Grose

True Stories A case of Mediterranean date louse in aircrew More tales from Masirah MJA 1998; 169: 651-652 Those of you who remember the "Caesarean section" described in the 1996 Christmas issue of the Journal will doubtless recall that I spent nine months during the mid-1970s with the Royal Air Force on Masirah, a desert island in the Arabian Gulf. It was not a posting that was highly sought after by any career-minded officer. Most of the people there knew of someone they had offended shortly before the posting notice arrived -- I had at least a dozen names on my list. Masirah had developed a slang of its own that had been handed on from generation to generation of those lucky enough to be posted there. For example, we were subject to a syndrome known as a "wobble". This could be anything from mild irritation on discovering that it was bloody crayfish for dinner again (sometimes known as a mini-wobble or "teeter") to a major affective disorder brought on by discovering that your replacement, due in seven days, had just thrown himself under a bus to avoid the posting. I once wrote a learned paper for distribution to section commanders on "The Wobble and how to deal with it when not in possession of live ammunition". It was well received, especially by the Padre, to whom the medical officers sent their incurable cases. Another of our local slang terms was a "rubber dick". The etymology is shrouded in history, but those of you who have served the Flag will be able to make a stab at it. It had come to mean a practical joke, the more devious the better. For many of the servicemen on Masirah, only just staving off alcoholism and insanity, the creation of rubber dicks had become their raison d'etre. This was true for none more so than the Medical Officers. One of our fellow officers thought it great fun to slip into someone's room, switch off the ceiling fan and place little heaps of talcum powder on the blades. When the victim returned to his room he would curse the heat, switch on the fan and spend the next 10 days dusting. We cured this fellow by the simple expedient of inflating a meteorology balloon in his room with a compressor hose passed through the window. When he returned and found that he couldn't open the door because the balloon had infiltrated every nook and cranny of his room, he resorted to stabbing the balloon with a kitchen knife through a tiny gap in the door. This was when he discovered we had filled the balloon with 10 kg of flour. My surgical colleague, GS, had been brought up without the company of dogs, resulting in a pathological fear of the species. As we were also the de-facto veterinary surgeons for the island, we were often consulted by the Chief Doggie (CD for short, but, more formally, the Flight Sergeant Dog Handler), who quickly saw my colleague's weakness and naturally sought ways to embarrass him. He told GS that one of the dogs had a very painful ear and was scratching and rubbing it. A vet would probably have prescribed antibiotics over the phone, but GS felt obliged to visit the dog section and attempt an otoscopic examination of the left ear of a 60-kg german shepherd called Rex. The "Doggies" couldn't wait to tell all and sundry about the pale, sweating "Doc" with his face 50 mm from a slobbering mouthful of teeth. They had a great laugh at GS's expense -- but they should have taken note of the glint in his eye. Some days later a signal (apparently) arrived for the Chief Doggie from his counterpart in Gan, another isolated station in the Indian Ocean. Masirah had just lent two dogs to Gan, and the signal said that the visiting dogs had come down with "a nasty case of anal strictures" and suggested that our dogs should be checked out, as the condition was "very infectious". Naturally, the first place our CD took advice was the medical section, which was only too ready to confirm the seriousness of the situation and offer advice on diagnosis. A somewhat white-faced CD left the medical centre with several examination gloves and a tube of lubricating jelly. Of course, we followed him back to the dog section and were peeking round the corner of the building when he completed the first examination, on Sheba, who at 40 kg was the smallest dog he could find. She was not amused, and let it be known in no uncertain manner. While we were looking forward to Rex's examination we decided that, as we would be the ones to suture the CD's wounds, we should probably admit to the rubber dick before any serious damage was done. The CD was so relieved that he forgot to swear undying enmity with the medical section. GS eventually served his time, and was sent home. He was replaced by DJ, who was living proof of the old adage that "You can always tell a Guy's man, but you can't tell him much". He was, however, the master of the rubber dick. DJ earned his spurs with a few notable ploys. He convinced the OC Admin Wing that paper mites were infesting the island and that he should not handle paper without rubber gloves. This reduced the number of minutes sent from his office by at least 90%. But we eventually had to own up when we were at risk of running out of gloves for surgery. DJ operated on one of the police dogs (with my anaesthetic) and became CD's hero. He operated on a camel and became my hero when it got "a bit light" and spat in his face. He won undying fame for successfully treating one of the Pakistani staff who had "gas in my stomach, which goes up through my heart to my head where it makes a ticking noise". (Diazepam 2 mg three times daily, should you ever come across the condition.) But there's no doubt that DJ's career best was the international vulcanised rubber dick of 1976. When DJ heard that we were to refuel a Vulcan bomber which was en route for the independence celebrations of a former colony, he decided that this opportunity for relief from boredom should not be allowed to pass. When the Vulcan joined the circuit to land, Air Traffic Control confirmed that its last port of call had been Cyprus. The pilot was cleared to land but told to taxi to the "disinfestation area" and await the arrival of the medical team. When the aircraft shut down, DJ, in full surgical garb, and backed up by every vehicle on the base that had a flashing light, plugged into the aircraft's intercom and spoke to the crew. He explained that there had been an outbreak of the Mediterranean date louse in Cyprus, and as dates were the only crop grown on Masirah the crew would have to be disinfested to satisfy local quarantine regulations. The pilot readily agreed to cooperate, and it was explained that the parasite was most commonly carried on the feet and hands. The crew were instructed to dangle their feet out of the hatch on the belly of the aircraft. Five pairs of desert boots appeared through the hatch and were duly sprayed with a sticky white powder from an ancient insecticide gun. They were then told to disembark, which they did, and DJ painted their arms from the elbows down with mercurochrome. So, with pink arms and white feet, they arranged with the ground staff for the refuelling of the huge bomber and headed for the mess for a nerve tightener. All parties were enjoying a drink when one of the crew sidled up to DJ and inquired quietly if there was anything else he ought to do to ensure his good health, as "I don't want to take anything home to the missus". This seemed like a good time to let them know they had been "had", and the party became more raucous than ever. They seemed to take it all with good grace, and left the next day, with appalling hangovers, for the independence celebrations. It was only after the Vulcan had been included in all the official photographs that the crew noticed the large phosphorescent orange cut-outs of a phallus our groundcrew had attached to both sides of the aircraft's tail. They seemed to take this with good humour too and, over another mammoth session in the mess on their way home, asked DJ for an official certificate of "disinfestation" as a memento for their crew-room in the United Kingdom. DJ and I thought this was the end of the matter, but two days later we were summoned to the CO's office. He slid a signal across the desk. It was from Principal Medical Officer, Strike Command. It said: "Understand you are taking precautions against Mediterranean date louse. State precautions and authority for use." The CO proffered the view that it was the glowing orange phallus that had done it, and suggested that our postings to Masirah should now be considered open-ended. Douglas N Gow Anaesthetist, Valley Heights, NSW Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Douglas N Gow

History Arterial disease in antiquity The study of papyrus writings and of mummified human remains provides an insight into the diseases and the practice of medicine in ancient times. Paleopathology, developed in the latter part of the last century and now incorporating modern technology and diagnostic techniques, has shown that arterial disease was not uncommon and that the arterial lesions of 3000 years ago were no different from those we see today. Reginald Magee MJA 1998; 169: 663-666 Introduction - Ancient Egypt - Vascular disease - Conclusions - References - Authors' details - - More articles on History Introduction In today's society there is a general awareness of arterial disease and its consequences. People know about coronary occlusions and strokes, and cholesterol has become a household word. In the press there are articles, almost daily, about diets, vitamins, forms of alternative medicine, the dangers of smoking and the advantages and disadvantages of consuming alcohol. Healthfood shops abound. The stresses of modern living have been implicated in arterial disease. While once senior executives worried about developing ulcers, now the concern is about coronary vessels and blood cholesterol. While we cannot be certain that the stresses we are subject to in our time are any greater than the stresses on primitive peoples and those who belonged to ancient civilisations, we do know they are different. Thus, in a context of different stresses, different lifestyles and different diet, it may be interesting to examine the occurrence of arterial disease in the past. Human remains in many countries have been examined by scientists, but those from ancient Egypt have probably been examined in the greatest detail. This article presents an overview of these studies in relation to arterial disease. Ancient Egypt In the 19th century there was an increasing interest in the ancient history of Egypt. Studies of ancient Egyptian writings, such as the Papyrus Ebers and Papyrus Edwin Smith (well known works on medical conditions and their treatment, written between 1500 BC and 2000 BC), and drawings and statues showing malformed people (Figure 1) have taught us much about disease and the practice of medicine in that civilisation. However, more direct information about diseases was obtained by the careful examination of skeletons and preserved tissue from unwrapped mummies. The unwrapping (or "unrolling", as it was often referred to) of mummies became a fashionable occupation in the last century. A number of mummies were investigated in 1834 by Thomas Pettigrew (surgeon to the Duke of Kent, whose chief claim to fame was that he vaccinated Queen Victoria). His efforts, however, made little contribution to the knowledge of disease in ancient Egypt as his unrollings were done rather hastily and the examinations were relatively superficial. It was in the latter part of the last century and the early part of this century that interest in the study of mummified tissue was regenerated with the development of paleopathology. This science was defined by Sir Marc Armand Ruffer, Professor of Bacteriology at Cairo Medical School, as "the science of diseases which can be demonstrated in human and animal remains of ancient tissues."1,2 Other notable workers in the field included Elliot Smith (Australian anatomist and anthropologist), Wood Jones (English-born professor of anatomy in Australia and Manchester), and the Egyptologist Margaret Alice Murray. Figure 1: Egyptian statue from the Old Kingdom (2686-2181BC of a person with exophthalmos. Embalming and mummification Ancient Egyptians believed that it was necessary to maintain the corpse in as lifelike a condition as possible, as the departed spirit would eventually return to the body. Thus, embalming was considered important and embalmers held some status within society. Today, we can preserve bodies by injecting fluid into the blood vessels, deep freezing and freeze drying. As these methods were not available to the embalmers of ancient Egypt, others had to be employed. The overwhelming evidence is that natron, a naturally occurring substance consisting mainly of sodium carbonate and sodium bicarbonate, was the main agent used. Three embalming methods (varying in thoroughness and in price1,3) are described in the writings of Herodotus (5th century BC) and Diodorus Siculus (1st century BC). These methods are summarised in Box 1. The study of mummies showed that embalming did not facilitate the opportunity for anatomical examination as the organs were removed roughly through a relatively small incision. 1: Embalming methods, in order of thoroughness and price, described in the writings of Herodotus (5th century BC) and Diodorus Siculus (1st century BC)The most expensive method involved physical removal of the internal organs (the brain by an iron hook passed up through the nose and the intestines and thoracic contents through a cut in the left flank, although the heart was often left as it was considered to be the seat of the mind), which were stored in Canopic jars and later may have been wrapped and returned to the body cavity. This was followed by cleansing of the cavities with palm wine and powdered aromatics, and filling of the body with myrrh, cassia and spices to add fragrance. The incision was either left, covered with a plate or occasionally sewn up. Muscles were removed through multiple small incisions and then the body was covered in natron for 70 days, then washed, wrapped in linen bandages and smeared with gum. Finally, it was returned to the relatives, placed in a case and kept in a sepulchral chamber. The next-most-expensive method was to fill the body cavity with cedar oil injected through the rectum and to cover it with natron for 70 days. On the last day the oil (which liquefies the inner parts) would be allowed to escape, leaving only skin and bone. The body would then be returned to the family. The cheapest method was simply to wash the body with a salt solution, embalm it with natron for the usual period and return it to the family for burial. Any extra filling required for the cleared body cavities was done with rags, sawdust or mud. Vascular disease Aortic calcification in two Egyptian mummies was first described by Czernak in 1852.4 The Australian Elliot Smith described tortuous calcareous temporal arteries in the mummy of Pharaoh Rameses II (XIX Dynasty, reigning 1279-1213 BC), and extreme calcareous degeneration, with the formation of large bone-like plaques, in the aorta of Pharaoh Mernephtah (XIX Dynasty). A sample of this aorta was sent to the curator of the museum at the Royal College of Surgeons, who made sections from it which he showed at a meeting of the Royal Society of Medicine in 1909.5Ruffer2,6 developed a method for preparation of the tissue sampled from mummies and examined a number of specimens from the XVIII to the XXVII dynasties (1580 BC - AD 527). In his article on arterial lesions, he commented on the extensive mutilation during the embalming process, when all of the viscera and most of the muscles were removed, so that it was only by accident that the whole or portion of the aorta or one of the large arteries was left behind.2 Thus, it was only the peroneal artery (and occasionally the arteries of an untouched arm or leg, remaining when the embalmers had not done their work properly) that was usually available for examination.2 He produced and published drawings of the gross and microscopic appearances of the specimens, some examples of which are shown in Box 2. 2: Coloured illustrations reproduced from Ruffer2 a. Pelvic and thigh arteries completely calcified. b. Calcified patches in an aorta. c. Calcified atheromatous lesion in a subclavian artery. d. Section through an almost completely calcified peroneal artery (van Gieson stain). * Remnants of endothelium and fenestrated membrane; † Calcified patches In 1972, Rosalie David, Keeper of Egyptology at the Manchester Museum, revived interest in the subject and involved many other scientific specialists in a study which became known as the Manchester Mummy Project.7 A range of multidisciplinary techniques were used in the examination of mummies, including radiology, computed tomography and magnetic resonance imaging, histological examination, electron microscopy, carbon dating, serological tests, DNA studies, fingerprinting, dental studies and scientific facial reconstruction. The team also pioneered the use of virtually non-destructive techniques, such as endoscopy, to obtain tissue samples. A mummy tissue bank has now been established at Manchester University's School of Biological Sciences to store samples from Egyptian mummies held in collections worldwide. In 1975, Aidan Cockburn and co-workers published the findings of an autopsy on the mummy known as Pum II (Pennsylvania University Museum mummy number II).8 The wrappings, resins and tissues were all examined in great detail. The aorta was found to contain large and small atheromatous plaques, and other vessels in organs returned to the body cavity in visceral packages showed some intimal fibrous thickening consistent with arteriolar sclerosis.8 Paleopathological studies of the vascular system of human remains preserved outside Egypt include those by Chinese pathologists examining the Mawangtui mummy, which was dated about 1120 BC.9 This was a mummy of a 50-year-old woman which had been immersed in a solution containing mercury salts, and sealed hermetically so that the fluid was still present. The arteries of this mummy, in particular the coronary arteries, showed atheromatous plaques and arteriosclerotic changes. Further, Zimmerman examined naturally frozen Alaskan mummies, the oldest of which (dated about AD 400) was of a 53-year-old Inuit woman who had moderate aortic and coronary atherosclerosis.10 More recently, the discovery of the body of a man estimated to be about 5000 years old near the Austrian-Italian border -- the "Ice Man" -- has become the subject of a book which describes the condition of the hair, skin and teeth.11 Although radiological studies have been done, macroscopic or microscopic studies of the internal organs have not yet been reported. There has been no study of arterial disease in Australian Aboriginal remains. This is, firstly, because their burial rites (which varied, but included often more than one of interment, mummification, cremation, platform exposure, delayed burial and burial in hollow trees) would have left little soft tissue for examination and, secondly, because of cultural sensitivities. It would, of course, be interesting to know to what extent arterial disease affected such an isolated and distinct race whose diet was simple, but characterised by indulgence at times of seasonal abundance.12 Unfortunately, paleopathological studies of Aboriginals have been limited to the study of skeletal remains which showed evidence of osteoarthritis, osteomyelitis and metastatic malignancy.13 Investigation of vascular disease Radiological examination of the mummies examined by the various pathologists showed calcification of the aorta, femoral and carotid arteries.7,8,10 High resolution computed tomography of the head of the Ice Man,11 whose estimated age was 35-40 years, showed "slight hardening of the arteries", presumably some calcification seen in the walls of the vessels, at the base of the brain. Macroscopic examination of mummies showed evidence of calcification of the arterial wall, which varied from isolated spots to bone-like plaques to rigid calcified tubes which would break when dissected out.2,6-9 Ruffer illustrated a specimen of subclavian artery which showed almost complete obstruction at its origin by thick calcified plaque. He also described arteries which appeared to be thickened and fibrous, rather like whipcord, but not calcified.2 Microscopic examination showed appearances of arteriosclerosis, atheroma, lipid deposition and medial calcification. Degeneration of the muscle coat and replacement by fibrous tissue was present in some specimens, and spots of calcification could also be seen.2,6-8,10 The elastic tissue could be easily demonstrated with such stains as phosphotungstic acid-haematoxylin and Heidenhain's iron haematoxylin, and among the degenerative changes seen was reduplication of the internal elastic lamina. Lipid could be demonstrated in plaque with such stains as Sudan 3 and 4 and Sudan black. Atheromatous lesions in mummy arteries have sometimes shown sectorial clefts, giving the impression of dissecting aneurysm.14 Figure 2: Section of a popliteal artery from a Ptolemaic mummy which shows that good tissue definition can be obtained, and that the intima media and adjacent fat are distinguishable, although intracellular details are not. Collagen and elastic tissues are the best preserved (courtesy of J T Rowling). Documented evidence of aneurysm Degenerative changes have been found in the aorta, coronary and peripheral arteries, but aneurysm has not been reported, probably because of the efficiency of the embalmers. However, Ghalioungui15 noted a description of aneurysm in the peripheral arteries in the Papyrus Ebers: "...a swelling of vessels ... it is hemispherical and grows under thy fingers at every going [ie, it pulsates], but if separated from his body it cannot become big and not come out [ie, diminish] ... it is a swelling of a vessel ... and it arises from injury to a vessel." (Eb 872) A cirsoid aneurysm (and the magic used to treat it) was also described: "...its appearance in growing on account of serpentining of the serpentry and they have formed many knots ... it is a swelling of vessels. Thou shalt not put thy hand to such a thing ... what is spoken is its effective spell 'flow out thy vessel ... that jumps in the midst of these limbs'." (Eb 873) It would appear that the lesions seen in the ancient Egyptians were no different from those we see at the present time in vascular surgery and morbid histology. Rowling, in his presentation to the Royal Society of Medicine in 1961,16 cited the mortuary inscription of Weshptah, the Architect, Vizier and Chief Justice of Pharaoh Neferirkere (2494-2345 BC), which suggested that he died of a cerebral haemorrhage. He also said that in the Papyrus Ebers there was reference to hemiplegia, and another to an association between disease of the vessels of the thigh and foot conditions which may have been gangrene. Rowling considered that it may have been fortuitous that the ancient Egyptians made this association. However, to read into this ancient text that disease of the vessels of the thigh was associated with gangrene would seem highly conjectural. Conclusions In his writings on Egyptian mummies, Ruffer speculated on the causes of vascular disease.2 He eliminated tobacco and syphilis, as neither was known in ancient Egypt. Although the Egyptians consumed both beer and wine, and did get drunk, as shown in ancient artworks, Ruffer's contemporary experience of over 800 autopsies in Muslim abstainers indicated to him that alcohol was not the cause of arterial disease. He considered meat consumption as a factor, but, while admitting that mummies represented the wealthier classes who may have eaten more meat than others, emphasised that the diet was mainly vegetable and, judging from dental wear, rather coarse. Ruffer also dismissed the stress of everyday life, as he did not consider the life of the ancient Egyptians to be any more arduous than at the time of his writing. His conclusion was that the causes of the degenerative disease were just as obscure in ancient times as they are now.2Disease has always been a part of life. Evidence of it has been found in the remains of reptiles of the Permian period through to the time when ancient human civilisations began to record it. It is clear that atherosclerosis is an ancient process, and its pattern has always been the same regardless of race, diet and the stresses of survival. However, in these days, modern man in may some ways encourage atherosclerosis by smoking and consuming foods with a high fat content. References Sigerist HE. Primitive and archaic medicine. Oxford: Oxford University Press, 1967. Ruffer MA. On arterial lesions found in Egyptian mummies. J Pathol Bacteriol 1911; 15: 453-462. Garner R. Experimental mummification. In: David AR, editor. Manchester mummy project 1979. Manchester: Manchester University Press, 1979. Sandison AT. Degenerative vascular disease in the Egyptian mummy. Med History 1962; 6: 77-81. Shattock SG. Microscopic sections of the aorta of King Mernephtah. Lancet 1909; 1: 319. Ruffer MA. Remarks on the histology and pathological anatomy of Egyptian mummies. Cairo Scientific J 1910; 4: 3-7. David AR, editor. Manchester mummy project 1979. Manchester: Manchester University Press, 1979. Cockburn A, Barraco RA, Reyman TA, Peck WH. Autopsy of an Egyptian mummy. Science 1975; 187: 1155-1160. Cockburn A. Miscellaneous mummies. In: Cockburn A, Cockburn E, editors. Mummies, disease and ancient cultures. Cambridge: Cambridge University Press, 1980. Zimmerman MR. The paleopathology of the cardiovascular system. Texas Heart Inst J 1993; 20: 252-257. Spindler K. The man in the ice. Guernsey, Channel Islands: Guernsey Press, 1995. Mulvaney DJ. The prehistory of Australia. Melbourne: Pelican Books, 1975. Webb SG. Paleopathology of Aboriginal Australians. Melbourne: Cambridge University Press, 1955. Sandison AT. Diseases in ancient Egypt. In: Cockburn A, Cockburn E, editors. Mummies, disease and ancient cultures. Cambridge: Cambridge University Press, 1980. Ghalioungui P. Medicine in ancient Egypt. In: Harris JE, Wente EF, editors. An x-ray atlas of the royal mummies. Chicago: University of Chicago Press, 1980. Rowling JT. Pathological changes in mummies. Proc Roy Soc Med 1961; 54: 409-415. Authors' details Princess Alexandra Hospital, Brisbane, QLD. Reginald Magee, FACS, FRACS, Senior Visiting Vascular Surgeon. Reprints: Dr H R Magee, "Alexandra", 201 Wickham Terrace, Brisbane, QLD 4000. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Reginald Magee

From shunned to shining: doctors, madness and psychiatry in Australian and New Zealand cinema Alan Rosen, Garry Walter, Tom Politis and Michael Shortland The histories of psychiatry and the cinema are eerily intertwined MJA 1997; 167: 640-644 Introduction - A psychiatrist's perspective - Films and psychiatric stigma - Conclusions - Acknowledgements - References - Authors' details - - - ©MJA1997 Introduction The motion picture industry has had a long-standing interest in doctors and medicine generally and with psychiatry in particular. Cinema's fascination with modern psychiatry has been intense, with the two fields emerging at about the same time -- movies were first demonstrated publicly by the Lumière brothers, Edison and others in 1895, the same year that Freud wrote Project for a scientific psychology, the prototype of his later theories.1 In 1924, the producer Samuel Goldwyn was keen to exploit the association between sex and psychoanalysis on screen and tried unsuccessfully to enlist Freud's help in making a film with an offer of $US100 000.2 Psychiatric professionals in films have been variously venerated, demonised and marginalised (classified by Schneider as, respectively, "Dr Wonderful", "Dr Evil" and "Dr Dippy"3). Hyler offers an even more elaborate and colourful classification for psychiatric patients in films: rebellious free spirit, homicidal maniac, female seductress, enlightened member of society, narcissistic parasite, and zoo specimen.4 Schneider contends that there has been a welcome shift over the years in the way film has treated madness and psychiatry, with oppressive psychiatrists and zombified victims giving way to more human encounters and ambiguous, even hopeful, outcomes.2 Arguably, however, the complete range of favourable and unfavourable stereotypes of psychiatrists and patients continues to appear -- 1991 saw the psychiatrists Dr Wonderful (Prince of Tides), Dr Evil (Silence of the Lambs ) and Dr Dippy (What about Bob?). Although the vast majority of "psychiatric" films are American (partly because the discipline is embedded in that country's culture), some of the most incisive movies, especially recently, have come from Australia and New Zealand. A chronology of antipodean films with psychiatric themes is shown in Box 1. While doctors and nurses have long been represented in antipodean films (e.g., Sister Kenny [1946]), the "psychiatric" film made its début only in 1974 with Between Wars. Michael Thornhill's first feature, a pioneer in the revival of Australian cinema, Between Wars traces the career of Dr Edward Trenbow (played by Corin Redgrave), who becomes a well-respected Sydney psychiatrist. In the 1920s, he takes up residence at Callan Park Asylum. The film touches on issues of psychoanalysis and physical treatments, such as fever treatment. In another 1974 release, 27A , a middle-aged "metho" drinker joins Alcoholics Anonymous and undergoes a psychiatric examination. As a consequence, he is committed to a hospital for the criminally insane, to be detained indefinitely under the notorious Section 27A of the Queensland Mental Health Act . Nevertheless, apart from these two films, the psychiatrist figure receives scant attention in the 1970s. When it appears, it is usually as either a peripheral character or a stereotype. The 1980s saw some clichéd psychiatric themes. For example, in An Indecent Obsession (1985) Sister Honour Langtree, in charge of a military hospital for psychiatric patients, transgresses boundaries by developing a sexual attraction for a new patient. Wrong World (1985) has the almost mandatory escape from a psychiatric hospital, and Contagion (1987) features a homicidal person with schizophrenia. The 1980s also saw the emergence of a film category which has been called "the company of eccentrics".5 Perversely non-conformist, it often foregrounded quirky protagonists and against-the-grain themes. For example, the hero in John Laurie's Stroker (1987) is "a kind of mad, Chelmsford psychologist", 5 and all the central characters in Bliss (1984) and Pandemonium (1987) seem in dire need of psychiatric evaluation. Some of Jane Campion's films also thrive on borderline heroines (e.g., the volatile Dawn in Sweetie [1989]). These eccentric personalities paved the way for the more stigmatised protagonists in the films of the next decade. An Angel at my Table (1990) depicts the life story of the award-winning novelist Janet Frame. The image of an apparently hopeless mental patient shimmers with that of a somewhat odd creative genius. Similarly, Heavenly Creatures (1994), about the relationship of two New Zealand girls who murder one of their mothers, provides a counterpoint between eccentricity and premeditated evil. Bad Boy Bubby (1994) also extends the "eccentric cinema's" preoccupation with idiosyncratic characters and offbeat themes. Except for the "soft" ending, it is totally uncompromising -- about an "uncivilised" innocent, Bubby, and his mother, who have been caught in an incestuous, symbiotic web for 35 years. On the return of his estranged father, Bubby is freed into a world which he cannot comprehend, a contemporary society which he views through an unsocialised, childlike perspective. Although there is no psychiatric intervention in Bad Boy Bubby and in other 1990s films such as The Piano (1993) and Once Were Warriors (1994), the relentless playing out of dark psychopathology might nevertheless be included in the "psychiatric" film category. Common to Australian and New Zealand "psychiatric" films in the 1990s is the more compassionate, sensitive handling of many types of intellectual and psychiatric disability,6 as illustrated by Domaradzki's Struck by Lightning and McKenzie's On the Waves of the Adriatic (named for the ancient Greek custom of casting mentally ill people adrift in boats on the Adriatic Sea). There is also a greater emphasis on more realistic, character-driven studies of madness -- Angel Baby, Cosi, Lilian's Story and Shine all strive for the narrative/dramatic depiction of alienated or troubled people for human interest. For example, Michael Rymer, the director of Angel Baby (about two people with psychoses, Harry and Kate, who fall in love), states that his film "is not about crazy people. It's about people who have an illness". 7 Cosi, based on Louis Nowra's play8 about a group of patients in an asylum who rehearse for and perform Mozart's Cos" fan tutte, has its American parallel in One Flew Over the Cuckoo's Nest (1975). We warm to many of the patients in both. Lilian's Story and Shine were inspired by real-life personalities supposedly driven mad by aggressive, possessive fathers. Lilian's Story is based loosely on the life of legendary eccentric Bea Miles, who recited Shakespeare for a dollar on the streets of Sydney and rode taxis for a sonnet. In Shine, Geoffrey Rush's portrayal of the pianist David Helfgott endears him to us, and the character ultimately triumphs in both his personal and professional life. Angel Baby, Cosi, Lilian's Story and Shine are not centrally critiques of institutions, but, rather, reinforcements of humanism and faith. The ambiguity of Angel Baby 's ending, in which we are unsure whether the hero suicides, is both tragic and potentially uplifting. Even so, we are left with a nagging feeling that this film missed its chance to instil hope because of the assumption that real-life mental illness must end in tragedy. Unfortunately, alongside the greater humanism and faith depicted in recent Australian and New Zealand "psychiatric" films, negative stereotypes about people with mental illness persist. These include the "homicidal maniac" (Doug, to staff member Lewis, in Cosi : "Hope you've made out your will, Lewis . . . you're mine"), "female seductress" (Cherry, in Cosi, also to Lewis: "I really like you", as she leans forward to kiss him), and the "zoo specimen" (Kate, in Angel Baby, resembles a feral animal as she hisses to frighten off shoppers at a mall). In addition, An Angel at my Table and Shine link madness with creative genius. While the general public may see this as instilling hope, or even as inspirational, people with mental illness may conclude that someone with a mental illness needs an exceptional creative talent to be accepted. A psychiatrist's perspective How accurately have films portrayed mental illness in terms of presentation, aetiology and treatment? From a psychiatrist's perspective, it is gratifying that the most recent Australian and New Zealand "psychiatric" films (Cosi, Angel Baby, Lilian's Story and Shine) have dealt with psychoses, which need better public understanding. However, better understanding is also needed for a range of stereotypically less bizarre disorders, such as depression and anxiety disorders, that are seemingly harder for film-makers to dramatise. Nevertheless, psychopathology has been displayed creatively and vividly in the recent films, including: auditory hallucinations (a tormented Harry clutching his head in Angel Baby); pressure of speech and flight of ideas (David Helgott, at a frantic pace in Shine : "I remember Margaret. She called me a pig. All very complicated; complicato in Israel, a battleground. A war zone, a war; what a bore it's a war . . . war"); delusions of reference (Kate, in Angel Baby, watching Wheel of Fortune on television, suggests that "Astral [on the television] sends me messages no-one else can understand"); poor social skills (Kate again, on first meeting Harry's family, flicks a whole chicken leg onto her dress and later suggests to Harry's sister-in-law, whom she has just met: "[Harry's the] best lay I've ever had . . . [he's got] a side manoeuvre from hell"); and lack of insight (Kate again: "I don't hang around with psychos -- I'm not psycho"; on the other hand, it could be seen as very sensible not to associate with stigmatised people if you wish to avoid being stigmatised yourself). The cinema imputes both genetic and environmental factors in the development of mental illness, consistent with current belief, but tends to emphasise environment. In Angel Baby, when Kate becomes pregnant she is advised by her doctor that "there's a chance that the child will inherit your illness". In contrast, Shine suggests that David's harsh upbringing contributed to his psychiatric illness, an oversimplification of the underlying themes and contribution of David's father. Nevertheless, while parenting practices are no longer thought to be instrumental in the later expression of psychoses, there is validity in the notion that stress can precipitate relapses and takes a toll on all family members. A range of treatments, both physical and psychological, have been portrayed. Lust and Revenge (1996) draws parallels between psychotherapists, religious gurus and market forces in the arts and, in the process, satirises all three. There is ambivalence about physical treatments. In Cosi, a patient about to perform in the opera reassures its director: "I'll be on top of it . . . I purposely didn't take my medication." In contrast, Kate, in Angel Baby, begs: "I want my Stelazine." However, psychotropic medication is also depicted as society's means of controlling undesirable behaviour and individuals, as attested by the comments of head nurse Errol Greer in Cosi : "The patients are on varying degrees of medication . . . don't let that worry you -- just worry about the ones who aren't." Electroconvulsive therapy (ECT) is represented neutrally in Shine but negatively in Cosi, where smoke billows from the ECT machine, and the patients are threatened: "Start making our sets [for the opera] or else it's back to shock treatment." Involuntary admission or sedation is also depicted. In Lilian's Story, the heroine is incarcerated for 20 years on the word of her sexually abusive father, and in Cosi the wrong person ("normal" Lewis) is injected with a tranquilliser without adequate assessment or consent. The community psychiatry movement has been discussed only briefly but disparagingly. Errol, in Cosi, states: "Half-way houses, community care . . . come on, the Government cuts the cost and chucks them [the patients] on the street." This negative misrepresentation of contemporary, integrated 24-hour community and hospital care can be partly explained by Nowra having drawn on his early work experiences in a psychiatric hospital in 1971. While this is made explicit in the introduction to the play, the film fudges the historical time frame so that the audience can easily assume this is current practice. Films and psychiatric stigma Recently, the National Mental Health Policy9 and the Burdekin Report10 have highlighted the need for attention to psychiatric stigma, and community surveys have revealed many public misconceptions about people with mental illness.11 Does the cinema influence psychiatric stigma, or is stigma so deeply ingrained in society that films cannot make a difference either way? Do film makers have a responsibility to teach or to change attitudes, or should we resign ourselves to the fact that films are essentially entertainment? Possible consequences of cinema depictions of mental illness and psychiatry (positive and negative) are shown in Box 2. Disturbing findings from the Glasgow Media Group12 show that public attitudes to mental illness are influenced more by media accounts of mental illness, which instil fear, rather than by direct contact with people with mental illness. Mindful that films and other media often depict people with mental illness as unpredictably violent, the Royal College of Psychiatrists organised a petition (signed by 3000 members) asking the media to alter their practices in the portrayal of mental illness and to develop guidelines.12 However, the response from producers and media managers was a deafening silence. So, is there any good news in film psychiatry? The relatively large number and appeal of recent "psychiatric" films from Australia and New Zealand is encouraging, as are the new messages of hope, resilience, rebellion, self-determination and triumph. In the most recent films, not only are people with mental illness portrayed as real characters capable of expressing the gamut of human emotions, but also a positive stereotype appears to have emerged -- the patient as hero or role model. The recognition of Janet Frame as a great writer in An Angel at my Table and David Helfgott's relationship with Gillian and celebrated return to the concert stage in Shine are a far cry from Kate in Angel Baby, who, sedated, make-up running and generally looking worse for wear, attracts the comment from her nurse: "She looks cute, doesn't she?". Moreover, An Angel at my Table and Shine show that mentally ill people can be examples for the community at large in how to persevere and transform adversity. Film makers and actors may assume that with the gradual improvements in psychiatric settings and treatments, which are becoming more sensitive to the individual, less intrusive and less disruptive to life, psychiatry will not offer sufficiently dramatic screen images. However, as Simon Champ, chair of the Australian Mental Health Consumer Network, pointed out (at a School on Psychiatry and the Cinema at the University of Sydney, New South Wales, in April 1997): "There is plenty enough drama available if you care to accurately tune into the subjective experience of an individual or family who has survived mental illness." Doctors, psychiatrists and other mental health professionals can help promote positive depictions of mental illness and psychiatry (see Box 3). Further, if there is some truth in the negative depictions of psychiatry in film, we can only hope that mental health professionals, rather than muttering darkly and dismissing the images, will reflect thoughtfully and use this as a stimulus to change their practice. Conclusions Ignored for so long, psychiatry and mental illness are now the subject of many films produced in Australia and New Zealand. These films should not be rejected simply as "quirky" or "harmless fun", but should be critically appraised to ascertain attitudes to patients, their families, their doctors and mental health professionals. Speaking in a Hippocratic vein, if a "psychiatric" film does no undeserved harm to these stakeholders and also entertains and has artistic merit, this is for the good. If the film is also accurate and informative, challenges prevailing attitudes and transforms your life, so much the better. Acknowledgements We thank Ronin Films, Roadshow Entertainment and REP Distribution for providing images from their films. We are also grateful to Karen Barfoot, Anne Deveson, Simon Champ and Julie Rigg. References Schneider I. Images of the mind: psychiatry in the commercial film. Am J Psychiatry 1977; 134: 613-620. Shortland M. Screen memories: towards a history of psychiatry and psychoanalysis in the movies. Br J Hist Sci 1987; 20: 421-452. Schneider I. The theory and practice of movie psychiatry. Am J Psychiatry 1987; 144: 996-1002. Hyler SE, Gabbard GO, Schneider I. Homicidal maniacs and narcissistic parasites: stigmatisation of mentally ill persons in the movies. Hosp Community Psychiatry 1991; 42: 1044-1048. Dermody S, Jacka E (editors). The imaginary industry: Australian film in the late 1980s. Sydney: Australian Film, Television and Radio School, 1988: 132-154. Hall S. Method in the madness. The Bulletin 1996 May 28: 80-81. Urban A. Angel baby. Cinema Papers 1995; 104: 12. Nowra L. Cosi. Sydney: Currency Press, 1992. Australian Health Ministers. National Mental Health Policy. Canberra: AGPS, 1992. Human Rights and Equal Opportunity Commission. Human rights and mental illness: report of the national inquiry into the human rights of people with mental illness. Canberra: AGPS, 1993. Commonwealth Department of Health and Family Services. Community attitudes to mental illness: qualitative research report. Canberra: AGPS, 1993. Philo G. Changing media representations of mental health. Psychiatr Bull 1997; 21: 171-172. Walter G, Rosen A. Psychiatric stigma and the role of the psychiatrist. Australas Psychiatry 1997; 5: 72-74. (Received 12 Sep, accepted 28 Oct, 1997) Authors' details Royal North Shore Hospital and Community Mental Health Services, Sydney, NSW. Alan Rosen, FRANZCP, MRCPsych, Director; Associate Professor, University of Wollongong; and Senior Clinical Lecturer, University of Sydney. Central Sydney Area Health Service, Sydney, NSW. Garry Walter, FRANZCP, Staff Specialist Psychiatrist and Inpatient Director, Rivendell Unit; and Clinical Lecturer, Department of Psychological Medicine, University of Sydney. WEA Film Study Group, Sydney, NSW. Tom Politis, President. University of Sydney, Sydney, NSW. Michael Shortland, PhD, Associate Professor of History of Science. Reprints: Dr G Walter, Psychiatric Stigma Study Group, Rivendell Unit, Hospital Road, Concord West, NSW 2138. - ©MJA 1997 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Alan Rosen · Garry Walter

Effect of postgraduate exams on putting performance MJA 1997; 167: 655 Objective: To test the hypothesis that examination stress adversely affects golf putting performance. Participant: An advanced trainee of a learned specialist college, with moderate golfing skills and about to undertake final fellowship examinations. Methods: A week before the exams, the subject was asked to perform 50 consecutive 60 cm putts on the practice putting green, under standard conditions. The hole was cut on a flat portion of the green, with negligible borrow or irregularities. The number of successful putts was recorded. Two weeks after successfully completing the exams, the subject was asked to repeat the test. The hole and the weather conditions were similar. Results: Test one. Successful putts: 40 (including three mulligans); unsuccessful putts: 10. Test two. Successful putts: 46 (including one mulligan); unsuccessful putts: 4. Mulligans were putts that, while not successfully "holed", were deemed by the subject to have been so close that they were considered "holed". Reasons included: "The wind changed direction at the last minute" and "The hole moved after I had putted". Statistical analysis: Two new techniques relevant to golfing data were used. The Norman Index of the sum of rank performances (n value) was multiplied by the Tiger Woods covariant of superior performances (t value). The resulting score was divided by the square root of the subject's handicap, giving a dubious value (d) which was statistically feasible (d < 0.05). Like all golfing data, these values need to be treated with suspicion. Discussion: The adverse affects of examination stress on putting performance could be a result of physical impairment (tremors and sleep deprivation) and psychological impairment (distraction and fear of failure). As putting is a vital component of a golfer's repertoire, it is reasonable to extrapolate that examination stress would be detrimental to overall golfing performance. It may be that poor golfing performances adversely impact upon examination performances. This requires further testing, preferably over a long period of time (several months would be fine), at a suitable golf course (perhaps Port Douglas in far north Queensland) and with appropriate funding (to cover travel expenses!). Conclusion: Examination stress adversely affects putting performance. Postgraduate examinations should be scheduled to avoid significant golfing fixtures, such as club championships. (Disclosure: Any resemblance between the author and subject is purely coincidental.) Craig T Hore Clinical Fellow, CareFlight, NSW Medical Retrieval Services PO Box 159, Westmead, NSW 2145 - ©MJA 1997 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Craig T Hore