History and humanities

This cheerful "Kilroy was here" image is a CT scan showing the grossly swollen scrotum of a young man after a motor bike accident.

Bit Lock Wong

An abdominal ultrasound of a patient with right iliac fossa pain revealed the culprit, smiling cheekily.

Khimseng Tew

When the patient presented with colicky abdominal pain we smelt something fishy. Abdominal ultrasound confirmed the diagnosis.

Nishantha S Karunaratne

Fetus in feto is a known phenomenon; could this be one? Or neural tissue in a dermoid cyst? Whatever, the patient appears well endowed, with the CT scan showing a spare brain and spinal cord in the thigh muscles.

Rodney H Strahan

This photograph was taken in Udaipur, Rajasthan, India, in 1988. It had occurred to me to submit it to the MJA some years ago, but I wanted first to be sure of the epidemiological validity of this omnibus statement.

Edward Brentnall

Fairfield Hospital, now sadly closed, once described as "an infectious disease training nirvana, where physicians danced naked along the banks of the Yarra", used to attract many returned overseas travellers with fever. Among the tens of thousands of blood smears screened by its excellent malarial scientists, occasionally a gem such as this "Australia antigen" was found. Note that Tasmania is represented by a platelet, rather than as part of the monocyte, surely reflecting the ambivalent status of our island State.

Robert Baird · Bronwyn Munro

To the Editor: I offer the following additions to the growing list of favourite books with a medical flavour.1,2 The house of God, by pseudo-intern Samuel Shem, is an irreverent, bawdy, cult classic ("Catch-22 with stethoscopes"). I was particularly intrigued by the "laws of the house of God", including "placement comes first" and "if you don't take a temperature, you can't find a fever." The woman who walked into doors, by Dubliner Roddy Doyle, is a heartrending narrative of emotional and physical abuse of a woman by her partner, and of neglect by her health professionals. "A nurse . . . She'd seen me before . . . I waited to be asked. Ask me. Ask me. Ask me. I'd tell them everything. Look at the burn. Ask me about it. Ask. No. . . Her boyfriend was waiting." "The doctor never looked at me. He studied part of me but he never saw all of me." Another is The plague, by French novelist Albert Camus and translated by Stuart Gilbert. " 'Please, doctor, what is it?' 'It might be — almost anything. There's nothing definite as yet.' . . . On returning to his flat [Dr Bernard] Rieux rang his colleague Richard, one of the leading practitioners in the town. "'No,' Richard said, 'I can't say I've noticed anything exceptional.' 'No cases of fever with local inflammation?' 'Wait a bit! I have two cases with inflamed glands.' 'Abnormally so?' 'Well,' Richard said, 'that depends on what you mean by "normal".' "

C Ross Philpot

A 35-year-old woman presented with symptoms suggestive of gallstones. These were confirmed on a computed tomography cholangiogram (see picture), the contrast clearly defining their outline. However, their unique "jack-o'-lantern" configuration also serves as a seasonal reminder that, like the present-day association with Halloween, the word "gall" derives from an Old English word meaning "something unpleasant to experience"!

Andrew D Wills MB ChB BSc MRCS

The United States will invest nearly US$70 billion (US$260 per capita) on medical research this year, more than half of which will be sponsored by the biopharmaceutical industry. This investment has been shown to provide major gains in basic, disease-oriented and patient-oriented research. It also provides a huge economic return on investment — whether measured in terms of jobs created, health costs saved, or the dollar value of lives saved. Australia, whose investment in medical research is less than 10% that of the United States, should increase its national commitment.

Leon E Rosenberg MD

Terry Spencer was born in Tenterfield, New South Wales, on 18 April 1917. He was brought up on a grazing property, where, because of isolation, education was difficult, but he was encouraged to read and absorb a wide range of information. He showed particular interest in mechanical matters, excelling in shooting with both rifle and pistol. After some years at Tenterfield Rural School and at "Shore" school in Sydney, Terry educated himself at home while working on the property, eventually passing his matriculation exams through the International Correspondence School at the age of 23. He enrolled in the Faculty of Science at the then New England University College, where he met his future wife, Margaret Cumpston. His studies were interrupted by the war. In 1940, he enlisted in the Air Force and trained as a radio and radar mechanic. Active war service contributed to the deafness that handicapped him in later life. When war ended, Terry was accepted as a medical student at the University of Sydney. After graduating in 1951, his first medical appointment was to Thursday Island, in the Torres Strait, where he took a special interest in diagnosis and treatment of tuberculosis in Indigenous people. It was there that his enduring interest in tropical medicine and insect-borne diseases began. In 1953, after gaining the Diploma of Tropical Medicine and Hygiene from the University of Sydney, he joined the Department of Health in Papua New Guinea. During his stay there (1953–1961), he became a specialist in the epidemiology and control of malaria. His expertise was recognised by his election as a Fellow of the Australasian College of Tropical Medicine in 1992. His other medical appointments included Visiting Medical Officer at the Prince Albert Memorial Hospital, in Tenterfield (1962–1974), and sole resident general practitioner in Werris Creek (1979–1987), a small town in northern New South Wales. Terry was a grazier, a malariologist, a great storyteller and a general practitioner with a wide range of abilities. Capable, conscientious and enthusiastic, with a quiet and friendly manner, whatever he undertook he carried out with integrity and to the best of his ability. He tackled all problems with courage and determination, not least his increasing helplessness in later years. He died on 15 February 2002. A loving and supportive husband and brother, Terry is survived by his wife Margaret and sister Anne.

Margaret Spencer OAM MSc PhD FACTM

"Early childhood asthma: what do we know and what do we need to know?" was debated by experts involved in paediatric asthma research and healthcare at the Macquarie Bank Asthma Australia Research Colloquium held in February 2002. The Colloquium, hosted by the Macquarie Bank Asthma Australia Research Alliance, offered a unique opportunity to consider important scientific, community and social issues relevant to children with asthma. This Supplement ...

Kay Patterson

Born on 18 March 1918 at Gundagai, in New South Wales, Eric De Salis came from a family that had a long association with the pastoral industry in the Monaro district of south-eastern NSW. His early schooling was at a family property, "Soglio", near Michelago. From 1930, he attended Canberra Grammar School, where he excelled in sport (tennis, athletics, cricket and football) and was both a prefect and dux of the school in his final year, 1936. Eric graduated in medicine from the University of Sydney in 1942. During his student years he met Dorothy Pratt, whom he married in 1943. From 1944 to 1946, he served Australia in the AIF as a medical officer with the field ambulance service in Papua New Guinea and Borneo. As one of the first Australian doctors to use penicillin in the field in Papua New Guinea, he described its effect as "miraculous" in helping desperately ill soldiers to recover in a remarkably short time. After the war, Eric worked in diagnostic laboratories at the School of Public Health at Sydney University, the Royal North Shore Hospital in Sydney, and the Commonwealth Health Laboratory in Townsville, where he became adept at the laboratory diagnosis of tropical diseases. He gained a Diploma in Public Health in 1946. In 1950, Eric was appointed Director of the Health Laboratory in Canberra. He expanded its clinical diagnostic services in haematology (his subspecialty), biochemistry and microbiology, and, in 1952, introduced a Pap-smear screening service (one of the first in Australia). He gained his Fellowship of the Royal College of Pathologists of Australasia in 1956. In 1965, the diagnostic laboratory was relocated to Canberra Hospital, where, in 1968, Eric was closely involved with Dr Bill Coupland in performing one of the first bone marrow transplants in Australia. Two years later, after recovering from a severe heart attack, Eric resigned as director of the laboratory, but continued to work as senior specialist in charge of haematology until his retirement in 1979. Eric developed motor neurone disease that progressed inexorably. This was a particularly cruel blow for a pathologist and for someone who had excelled in sport. He bore the pain and the restrictions imposed by the disease without complaint, showing a quiet fortitude and remarkable courage up to the time of his death on 14 February 2002. Eric's selflessness and modesty as a professional colleague were widely acknowledged, as were his skills in many fields of pathology and his prompt response to calls for assistance, at any hour, at Canberra Hospital. He was respected by all who knew him.

Anthony J Proust FRCP FRCPE FRACP

Henry Hudson was born in Santiago, Chile, on 2 February 1933. He studied medicine at the University of Chile, graduating in 1959. In the same year he began a residency at the Institute of Neurosurgery in Santiago under Professor A Asenjo, cofounder of the prestigious Journal of Neurosurgery. From 1966, under a British Council scholarship, he did postgraduate work in neurosurgery at the University of Edinburgh, Queen's Square Hospital (London) and the Radcliffe Infirmary (Oxford). In 1969, Henry returned to the Institute of Neurosurgery in Chile as a neurosurgeon. Two years later, the worsening political and economic situation in Chile led him to accept an invitation to come to Australia to work as a Neurosurgical Registrar at Sydney's Royal Prince Alfred Hospital. In 1974, he gained Fellowship of the Royal Australasian College of Surgeons in Neurosurgery, and in the following year began work at Concord Hospital (at the time, primarily a hospital for war veterans). It was at this hospital, with numerous patients suffering from back problems, that, 10 years later, he began to develop a unique specialty in microneurosurgery of the spine. By 1994, he was Head of the Department of Neurosurgery, but he retired in April of that year to work full-time on the development of microneurosurgery of the spine at the Mater Misericordiae Hospital in North Sydney. Using the operating microscope, specially developed surgical instruments and a rigid diagnostic protocol, Henry (with supporting radiologists) was able to precisely locate compressed nerve roots in the lateral recess of the spine and decompress them in a manner that was minimally invasive to the surrounding muscles and tissue. He took a keen interest in developments of the procedure in the United States and Europe, where it has become the procedure of choice. By limiting the size of the incision and reducing the operative damage to the paravertebral muscles, he enabled his patients to recover with less pain and at a much faster rate than they would have after conventional surgery. The procedure reduced postoperative complications from the usual 4% to around 1%. It was of particular value for patients who were elderly or unwell, and revitalised the careers of many professional footballers. Henry died of cancer on 4 November 2001 and is survived by his wife, Ana Maria, and children Paul, Henry and Mary Ann. To the end he was a caring man, a humanitarian, a brilliant surgeon and a true gentleman, who deserves his place in the annals of medical history. He was made a Member of the Order of Australia posthumously in the 2002 Queen's Birthday Honours list for "service to neurosurgery, particularly as a pioneer of minimally invasive surgical techniques for spinal conditions".

Paul Hudson

Richmond Rikard-Bell, a pioneer in the field of human sexuality studies, was born on 25 April 1922 in Sydney. He was educated at the King's School, Parramatta, and enrolled in medicine at the University of Sydney in 1941. When war broke out in the Pacific in 1942, he took leave from his medical studies to enlist in the RAAF and saw active service in the Pacific. He completed his medical degree in 1950. Richmond worked as a Resident Medical Officer at St George Hospital, then spent five years in a country practice at Captain's Flat, near Canberra. He then moved to Sydney, where he established the first medical practice in the Peakhurst–Lugarno area, as well as a practice at Brighton-le-Sands, where he remained until his death. It was a family practice with a strong emphasis on mothers and babies. Early on, he noted that the young couples whose babies he delivered were often extremely ignorant about marriage, birth and sexual technique, and that this often led to much unhappiness. In setting out to rectify this, he became a pioneer in the field of human sexuality studies, giving courses of instruction to young couples and lecturing at the University of New South Wales to third- and fourth-year medical students. His book, Loving sex, published in 1991, has been widely acclaimed by the public and members of the medical and allied professions. He regarded this as his life's work. Richmond married Joan Davies in 1945 and had a very happy family life with his own six children and two adopted children. The medical tradition in his family is continued by three sons who have become outstanding doctors. Richmond had a lifelong interest in cricket and overseas travel. Although his last years were marred by periods of ill health, he never allowed these problems to affect his happy disposition and interest in his work and hobbies. Diagnosed with carcinoma of the colon, he faced his illness with fortitude and a positive attitude, seeing patients until the end. He died on 19 November 2001.

Ian S Collins FRACP FRCPE FRCP

To the Editor: It was a most interesting idea to call for a list of favourites books.1 I have some of my own to add. The death of Ivan Ilyich, by Tolstoy — all the different responses to a dying man handled in the way only Tolstoy can. Interestingly, the most comforting presence was that of his illiterate man-servant, Gerassim. The doctor, his patient, and the illness, by Michael Balint — this was introduced to me by a very thoughtful medical student when I was a surgical registrar in England 40 years ago. A new edition edited by Balint's son has appeared in the past year or two. Contrary imaginations, by Liam Hudson — the advice in this book on selecting medical students and introducing first-year students to clinical medicine is now being carried out by many teaching schools 35 years after it was written! A long season in hell, by Gail Graham — the story of a mother's fight to rehabilitate her head-injured son. This book has all the characters that a doctor should be aware of — good doctors, bad doctors, unimaginative bureaucrats and politicians, helpful people and an inspiring physiotherapist who lost her husband, apparently through suicide, during the period she was fighting for her son. The book would be an ideal seminar topic for medical students and ethics discussion groups. Lastly, Intellectual impostures, by Sokal and Bricmont — a book with little medical content, but which should be read by every intelligent person. Sokal submitted pretentious gobbledygook to a postmodern journal, which was published. He then exposed the hoax, creating an enormous stir. This book is an expansion of that exposure.

Aubrey W Jansz

To the Editor: I read with interest the article by Goldsworthy and McFarlane on Howard Florey, Alexander Fleming and penicillin.1 With regard to the cause of Florey's "famous pinched smile", which allegedly hid tooth erosion caused by his drinking dilute hydrochloric acid prescribed for achlorhydria, a more prosaic yet interesting explanation is found in the memoirs of Raymond Valentine Hennessy. Hennessy was Senior Ear, Nose And Throat Surgeon at St Vincent's Hospital, Melbourne, between 1928 and 1951.2 Howard Florey in the late 1930s In August 1936, Florey, who was then Professor of Pathology at Oxford, visited his dying mother in Melbourne. He and his family stayed with his sister, Dr Hilda Gardner. Florey had a supply of sulfanilamide, probably the first in Melbourne, to treat his daughter, who was convalescing from a recent mastoid operation. During his stay, Florey attended a local dentist for treatment of a painful lateral incisor tooth. Some days later (on a Saturday evening), his face had become swollen and he began having rigors. His sister, a medical graduate who was then working as a clinical pathologist and microbiologist at the Melbourne Hospital, appreciated the danger — an abscess of a lateral incisor tooth can produce a cavernous sinus thrombosis — and quickly contacted Raymond Hennessy, who lived nearby. Hennessy had graduated as a dentist before pursuing a career as an ear, nose and throat surgeon and had written about the dangers of a lateral incisor dental abscess.3 After examining Florey, Hennessy told him that the offending tooth required extraction that night. Initially, Florey refused to heed his advice, preferring to see his own dentist the following Monday. Fortunately for Florey, he was persuaded by his sister to have the extraction. Hennessy then telephoned a dentist colleague, and they all met at the latter's surgery in Collins Street, where Hennessy gave Florey a gas–oxygen anaesthetic, and the nervous dentist proceeded to extract the incisor. However, he extracted the normal central incisor, not the offending lateral! On realising his mistake, the dentist "went to water", but Hennessy immediately rose to the occasion and extracted the correct tooth. When Florey woke from the anaesthetic, as Hennessy well remembered, he was not amused. Later, he had a dental plate made but did not like wearing it. Whether he took the sulfanilamide is not known. This episode is not mentioned in Gwyn Macfarlane's biography of Florey.4 However, the photograph of Florey in the frontispiece of this book shows the gap in his upper incisors (pictured). I believe this is the explanation for Florey's "famous pinched smile".

Ivo D Vellar · Thomas B Hugh

To the Editor: The patronising article by Goldsworthy and McFarlane on the discovery of penicillin1 depicts the popular heroic view of Alexander Fleming as a myth, but also promulgates myths of its own. Their description of the Fleming saga is historically accurate. Fleming searched for an answer to the riddle of infection, and, to paraphrase Pasteur, chance in the form of a spore of a rare subtype of Penicillium favoured his prepared mind. Whether or not the spore came through an open window is irrelevant, but the windows in Fleming's laboratory — now preserved as a museum (pictured) — could be opened3 and probably were on occasion, as Fleming was a heavy smoker. Fleming perceived the significance of inhibition (or, more correctly, lysis) of staphylococcal colonies, named the active agent "penicillin" and studied its effect on animals. Goldsworthy and McFarlane are "astonished" that he failed to inject it into infected animals to investigate its therapeutic effect, but the reason is simple: Fleming discovered that penicillin was rapidly inactivated by serum, dashing his hopes for its use as a systemic agent.3 Although he met opposition from his chief, Almroth Wright (known to his students as "Almost Right"), who rejected the view that penicillin might be a useful therapeutic agent, it is absurd to say that Fleming was "a victim of the pessimistic mind-set against toxic chemical antimicrobials". His confidence in its lack of toxicity led him, in 1929, to use penicillin to treat pneumococcal conjunctivitis in one of his assistants, with dramatic success.2 Site of Fleming's laboratory The Clarence Wing, St Mary's Hospital, London, in 1910. Fleming's laboratory, where penicillin was discovered in 1928, was on the third floor of the tower on the right. The windows of the laboratory could be opened by an internal system of ropes and pulleys, but a more likely source of the Penicillium spore was a dumb-waiter shaft communicating with a mycology laboratory on the floor below.2 To say that "Fleming had little idea what to do with his mould apart from dabbing it on infected wounds" unfairly trivialises his actions after the discovery. In addition to clinical and animal studies, he had the mould identified, deposited a culture with the collection held by the Medical Research Council and published his observations. He set two researchers to work purifying the active principle of the mould broth, and established that penicillin was soluble in alcohol and that its stability was pH-dependent. He also developed an assay for penicillin and defined the range of organisms that were sensitive to it. He sent cultures of the penicillin-producing strain to many laboratories, including Oxford, where that very culture later provided the starting point for Chain and Florey's work. Fleming's subsequent work on penicillin was stalled by his lack of biochemical expertise; he was unable to overcome the difficulties of purification and stabilisation.2 Fleming is recorded as saying, "It's up to the chemists now, I'm no chemist".2 It is quite untrue that "he then effectively forgot about it for 13 years". Although Fleming ceased clinical work on penicillin in 1934, he continued with laboratory studies. A contemporary at St Mary's Hospital, Dr A G Cross, recalled that in the 1930s "penicillin was on his mind all the time and in the minds of those who worked with him".2 Fleming had his faults, but the genius of his prepared mind did indeed present humanity with a fairy tale come true. Perhaps Ernst Chain, who did not particularly like Fleming, should have the last word: "There is no doubt that this discovery, which changed the history of medicine, has justly earned [Fleming] a position of immortality."2

Ivo D Vellar · Thomas B Hugh · Peter D Goldsworthy MB BS · Alexander C McFarlane MD, Dip Psychother, FRANZCP

In reply: Our article aimed to show how history is often rewritten in narrative forms that are more appealing to the human need for heroes and for clear, memorable moral lessons.1 The challenge is to sort out whether the matters at stake are those of narrative style or substantial differences of fact. Hugh felt our approach was patronising to Fleming — but we were at pains to emphasise his "genius" for making important causal connections. He also had a genius for seeking adulation — which in no way disqualifies him from deserving to share the Nobel Prize for Medicine with Chain and Florey. Hugh also criticised our assertion that "Fleming had little idea what to do with his mould apart from dabbing it on infected wounds" — yet his counterexample, that in 1929 Fleming used "penicillin to treat pneumococcal conjunctivitis in one of his assistants", illustrates the point. Let us also not forget that a Belgian group had discovered the penicillin mould in 1920, and recognised its antimicrobial properties well before Fleming did. The challenge is to foresee and drive the application of knowledge rather than to leave facts in a dormant but pregnant state. Vellar's fascinating letter proposes that a dental abscess and two extractions, rather than Florey's drinking of hydrochloric acid, caused his "pinched smile". A mutually compatible hypothesis is that Florey was prone to this infection because of tooth damage caused by the acid. Vellar also provides further support for the quixotic spread of knowledge and the personal motivations and obsessions that influence researchers. Florey's transport of sulfanilamide to Melbourne was apparently not to popularise the new and revolutionary drug, but to treat his daughter. It also raises a fascinating, if ironic, possibility: was Florey's life saved by sulfanilamide, allowing him to continue on his yet-to-be-forged endeavour of the purification of penicillin?

Ivo D Vellar

Although most naturally occurring infections with anthrax and plague are cutaneous, both organisms are most likely to be deliberately disseminated in aerosolised form, resulting in severe pulmonary illness. Mortality from both would be high and rapid in the absence of early and effective treatment, making swift and effective liaison between alert clinicians and public health authorities crucial to an effective response. Differentiating features include mediastinal widening (anthrax) and haemoptysis (plague). Doxycycline and ciprofloxacin are effective agents for prophylaxis and treatment for both diseases. Medical advocacy for strengthening the Biological Weapons Convention, particularly with an enforceable protocol including verification and compliance provisions, is needed.

Michael Whitby FRACP, FRCPA · Tilman A Ruff MB BS(Hons), FRACP · Alan C Street MB BS, FRACP · Frank Fenner MD, FRS

Emeritus Professor Wallace Ironside, Foundation Professor of Psychological Medicine at Monash University, Melbourne, died in Sydney on 19 July 2001. He was a pioneer of academic psychiatry in New Zealand and Australia. Wallace Ironside was born in China on 31 July 1917. After undergraduate medical training at Aberdeen University and war service in Italy, he trained in psychiatry at the Royal Aberdeen Infirmary (1946–1947) and worked at the Crichton Royal Hospital in Dumfries, Scotland (1947–1949), where Douglas McCalman and W Mayer-Gross shaped his lifelong interest in developmental and dimensional issues of psychopathology. He was a lecturer at Leeds University, UK, from 1949 to 1952. From 1959 to 1960, as a Fellow in George Engel's Department of Psychiatry in Medicine at the University of Rochester, New York, Wallace consolidated his special interest in liaison psychiatry and medical education. Engel's biopsychosocial model became the basis of integrated medical education in the Western world. Wallace promoted Engel's model when appointed to the Foundation Chair of Psychological Medicine at Otago University, Dunedin, New Zealand, in 1953, and later to the Foundation Chair of Psychological Medicine at Monash University, Melbourne, in 1969. There, he initiated a teaching program that had medical students considering psychosocial issues from their first day and following the psychosocial health of families over time. With clinician colleagues, he initiated a training program for psychiatrists that was based in general hospitals rather than psychiatric institutions, and had them enrol in a Master's degree in Psychological Medicine. His research focused on emotionally deprived children. Wallace was President of the Royal Australian and New Zealand College of Psychiatrists from 1972 to 1973, and cofounder and inaugural President of the Victorian Association of Psychoanalytic Psychotherapists, 1975–1976. He served on a number of hospital boards and National Health and Medical Research Council committees. After retirement from Monash University in 1982, Wallace continued his academic and clinical activities for a further seven years, retiring from these only when his hospital, Prince Henry's, was demolished and its functions relocated to Monash Medical Centre. There, his influence is still strongly felt: the Centre is a bastion of liaison psychiatry that continues the fight to have all patients seen as integrated human beings with biological, psychological and social needs. A new generation of students and psychiatrists receive this wisdom; this is Wallace Ironside's memorial.

Graeme C Smith MD DPM FRANZCP

Collaboration between industry and academia is becoming increasingly prevalent and successful in Australia. To encourage and foster these relationships while preventing excesses, Australia needs to act now to create ethical, legal and legislative frameworks for collaboration. As the United States has progressed further than Australia in fostering and controlling collaboration between industry and academia, Australia has the opportunity to learn from the US experience. To speed the pace of development, Australia needs to consider making changes to legislation and increasing the level of government funding, either directly or by the creation of incentives for investment of venture capital and superannuation funds in biotechnology.

Hamilton Moses III MD · Abbey Perumpanani MD, PhD · Jon Nicholson MBA

John St George was born in Malaya on 2 December 1924. His family returned to Ceylon in 1925, where he studied at St Patrick's College in Jaffna. In 1950, he graduated with Honours in medicine from the University of Ceylon in Colombo. Between 1957 and 1959, John worked with Professor T Jeffcoate at the University of Liverpool, UK, then with Dr P Myerscough at the Eastern General Hospital, Edinburgh. He was accepted as a Member of the Royal College of Obstetricians and Gynaecologists (1958) and a Fellow of the Royal College of Surgeons (1959), the International College of Surgeons (1968), and the Royal College of Obstetricians and Gynaecologists (1970). After working as a Consultant in Obstetrics and Gynaecology for the Government of Ceylon from 1959 to 1964, John spent a number of years (1964–1967 and 1972–1975) as Chief Consultant in Obstetrics and Gynaecology for the government of northern Nigeria. It was there that he perfected his technique of vesicovaginal fistula repair. These fistulae, which are relatively common among rural women, arise from obstructed labour or from application of potassium permanganate by "bush doctors" (local herbalists). While in Nigeria, John initiated the obstetric "flying squad" to enable women in remote areas to receive emergency medical treatment, and helped to invent a two-wheel collapsible trolley for bush track roads to help reduce maternal mortality. In 1974, the London School of Hygiene and Tropical Medicine awarded him the Langley Memorial Prize for this work. In 1975, John migrated to Australia and set up practice at Burwood and Lakemba, in Sydney, working as a gynaecologist at the Western Suburbs Hospital until 1993. He retired in 1998. John was passionately interested in sports and the Church. From his early years at St Patrick's College, where he was the captain of both the athletics and soccer teams, he took to heart the College's motto "fide et labore" (faith and work). He based his entire life on this simple yet profound philosophy, which saw him succeed in his career and adapt to many different cultures and countries with ease. John died peacefully (of hypostatic pneumonia) at Concord Hospital on 9 December 2001, at the age of 77.

Lourdes I St George LRCPS FRCOG FRACOG

To the Editor: The Australian Defence Force (ADF) has sustained many cases of malaria following service in East Timor.1 To reliably prevent relapse of malaria caused by the Chesson strain of Plasmodium vivax present in this region, larger doses of primaquine are required2 (up to 6 mg/kg total dose,3 compared with > 3.5 mg/kg to prevent relapse of sub-Saharan vivax malaria4). The ADF uses 1500 mg chloroquine (total base) followed by 315 mg primaquine (total base) for the treatment of vivax malaria, which, in Australia, is commonly treated either without primaquine or with inadequate dosages of either chloroquine or primaquine.5 A fit, 65 kg male soldier who deployed to East Timor from October 1999 to May 2000 experienced one episode of vivax malaria during his deployment and a further four episodes on return to Australia (Box). Having had malaria in East Timor, he complied closely with postexposure prophylaxis with primaquine and tolerated his dose (7.5 mg three times daily with meals) well for the required 14 days (315 mg total). He was seronegative for HIV, hepatitis C, and dengue IgG and IgM, and was not glucose-6-phosphate dehydrogenase deficient. The Table shows that our patient had a parasite that was apparently responsive to chloroquine, although it did not respond as readily in the last episode. In his first episodes of malaria on return from East Timor, he received the recommended dose of primaquine, but developed recurrences in the absence of further exposure to malaria. These relapses presumably indicate an inadequate response to the primaquine. The total dose of primaquine used for postexposure prophylaxis and treatment of the first episodes in Australia was about 4.8 mg/kg. He has subsequently received a treatment of 6 mg/kg total primaquine (see Table, Episode 5). This follows extended suppression with chloroquine before and doxycycline during a three-month deployment to Malaysia. There has been no further relapse six months after treatment. Chesson-strain vivax malaria is known to be difficult to treat and in which to prevent further relapse. Adequate primaquine to treat vivax malaria from other areas is not adequate for that contracted to the immediate north of Australia. Relapsing vivax malaria from East Timor may require a dose of 6 mg/kg of primaquine to prevent further relapse. Parasite density and treatment during the patient's episodes of malaria Episode Date of diagnosis Parasite density Treatment 1 1 April 2000 Positive on immunochromatographic test* Chloroquine 1500 mg, continued doxycycline 100 mg daily, primaquine 315 mg from 2 May 2 17 July 2000 23 000/µL Chloroquine 1500 mg, then primaquine 315 mg 20 July 2000 No parasites seen 3 26 Sep. 2000 8607/µL Chloroquine 1500 mg, then primaquine 315 mg 29 Sep. 2000 No parasites seen 4 11 Dec. 2000 11 400/µL Chloroquine 1500 mg, then weekly for two months† 14 Dec. 2000 No parasites seen 5 3 April 2001 Occasional trophozoites on thick and thin film Chloroquine 1500 mg, then weekly for one month; doxycycline for three months, then primaquine 420 mg 6 April 2001 Occasional trophozoites only on thick film * Immunochromatographic test used in the field. † Patient ceased treatment.

Scott J Kitchener · Isaac Seidl

Australia lost one of its eminent academic surgeons when John McCaffrey died of cancer on 4 November 2000. Ironically, as an oncological surgeon he had treated many grateful cancer patients during his long and distinguished career in south-east Queensland. John was born on 31 January 1933 and educated in Brisbane at St Lawrence's College, where he was school captain, school dux and captain of athletics. He graduated from medical school at the University of Queensland in 1956 with first class honours and also received the University Medal for Outstanding Merit, the Nathanial Robertson Medal in Medicine, and the H G Wilson Prize. John started his medical career in 1957 at Brisbane's Mater Hospital, where he met and later married physiotherapist Denise Moroney. He completed a Master of Surgery in 1961 and became a Fellow of the Royal Australasian College of Surgeons in 1962. In the same year he won the prestigious Nuffield Travelling Fellowship, which he took up at the University Department of Surgery in Glasgow, where he remained for two and a half years and passed his Fellowship of the Royal College of Surgeons. Returning to Brisbane in 1964, he was offered the post of Senior Lecturer in Surgery at the Royal Brisbane Hospital and was promoted to Associate Professor in Surgery in 1969 at the Greenslopes Repatriation Hospital. In 1985, he was appointed Mayne Professor of Surgery, University of Queensland at the Royal Brisbane Hospital, a position he held until his retirement in 1989. John not only demonstrated a tremendous intellect, but also displayed great compassion for his patients and an excellent rapport with his students. He undertook a substantial body of clinical and scientific research in the course of his career and made an enormous contribution to surgical knowledge. He published over 100 scientific publications and was the author of numerous book chapters and many films and video clips. He had a vast number of international surgical contacts and was well known professionally in the United Kingdom, Europe, the United States and Canada, as well as many countries in Asia, particularly Vietnam. He was a founding member and eventually President of the Australian Society of Ultrasound in Medicine. He had a long association with the Queensland Cancer Fund (QCF) and was Chairman of its Medical and Scientific Advisory Committee from 1985 until the time of his death. His generosity of spirit was demonstrated by the enormous time he dedicated to the QCF with no financial reward. John was founder of the Breast Screening Clinic at the Royal Women's Hospital, Brisbane, which opened in 1985 as the first public breast screening service in Australia. Its operating principles were incorporated into an Australia-wide pilot study, on which the BreastScreen Australia program was eventually based. In the course of his career, John made a very substantial contribution to the development and progress of surgery and surgical oncology, both in Australia and internationally. In particular, he advanced the understanding and implementation of breast cancer screening and of the treatment of early breast cancer, and disseminated his knowledge as a dedicated teacher and researcher. He is survived by his children Anne-Marie, Elizabeth, Sean and Chris.

Ian C Bennett

The use of biological agents as weapons of war is not new. In the 14th-century siege of Kaffa, on the Black Sea, the attacking Tartars catapulted bodies of plague victims at the defending Genoese, who contracted the disease and abandoned the city. Over the past century, many countries have developed the capacity to use biological agents to produce casualties in humans and domestic animals and to damage crops and environmental systems. Some biowarfare programs are known to have continued despite the adoption by 144 countries of the 1972 Biological Weapons Convention, which prohibited development or acquisition of such weapons. Early recognition of unusual clinical illness by physicians is an integral part of the public health response to a biological attack. We review the features of four biological agents of greatest concern. In this article, we discuss smallpox, a disease not seen in the world for the past two decades, and botulism. A subsequent article will discuss anthrax and plague. SmallpoxEpidemiologyIn a world declared free of smallpox in May 1980,1 this disease has characteristics that make it particularly suitable for biological warfare. It can be spread person-to-person. With the cessation of vaccination programs over 20 years ago, immunity has waned among those who have been vaccinated, while those born since 1980 are unvaccinated. The virus spreads by the respiratory route (primarily by droplet nuclei or aerosols expelled from the nasopharynx of infected people) or by direct contact (being released from ulcers on the oral mucosa from the time lesions appear on the skin and two to three days after onset of fever). It has also been transmitted by soiled clothing and blankets used by patients. Smallpox spreads rapidly between close family contacts2 and within hospitals when no special precautions are taken.3 Smallpox as a weaponOther features of smallpox that contribute to its suitability as a weapon are the stability of the virus in aerosol form and the likely small infective dose.4 Smallpox virus was added to the biowarfare program of the Soviet Union in 1980. Successful methods of stockpiling large amounts of this virus and delivering it from aircraft or ballistic missiles have been developed.5 With the discontinuation of the Soviet civilian biowarfare program in 1992, hundreds of experienced scientists became available to sell their services and take smallpox virus to other countries.5 The Indian strain of smallpox virus, used in the Soviet biowarfare program, causes a mortality of about 30% in unvaccinated people. Clinical features and diagnosisThe incubation period of 10–14 days ends with sudden onset of fever, headache and backache, usually severe enough to confine the patient to bed. Fever usually continues as the rash develops, with pain associated with pustule growth. Scabs develop and gradually separate, leaving pitted scars. The rash is the most important feature allowing early recognition of smallpox (Box 1). Most cases have been "ordinary type" smallpox, which has pustular lesions, but variant forms ("flat" and "haemorrhagic type" smallpox) occurred rarely and were almost always fatal. Modified smallpox occurred in people with waning immunity after vaccination and those who were vaccinated very early in the incubation period, and comprised a few skin lesions, which evolved more rapidly than those in unvaccinated people. Clinical diagnosis can be confirmed by electron microscopy of vesicular or pustular fluid or scabs, which should be collected and processed under maximum containment conditions. Management and preventionThe only proven effective treatment for smallpox is vaccination before or within three days of exposure, which may abort or modify the severity of an attack. Other treatment is supportive only, plus antibiotic therapy if secondary bacterial infection develops. Strict quarantine with respiratory isolation for 17 days is required of all cases and direct contacts of index cases. Vaccination with vaccinia virus is effective in preventing smallpox for at least five years and may prevent or modify infection for a much longer period, but this varies greatly from person to person. However, very few doses of vaccine are available worldwide at present. Furthermore, smallpox vaccination is associated with more severe adverse effects than any other type of vaccination: for example, encephalitis occurs at a rate of one per 300 000 primary vaccine doses and a quarter of cases are fatal, with some survivors having permanent neurological deficits.4 Therefore, both the World Health Organization and the United States Centers for Disease Control and Prevention have recommended that it should be used only to contain suspected cases and not for mass vaccination.6 BotulismEpidemiologyBotulism is extremely rare in Australia, with no reported foodborne cases since 1991.7 The causative organism, Clostridium botulinum, is an anaerobic, spore-forming, gram-positive rod found in soil (Box 2). It produces a potent neurotoxin that causes paralysis of skeletal and smooth muscle by interfering with acetylcholine release at the neuromuscular junction. Botulism as a weaponBotulinum toxin was first developed as a biological weapon over 60 years ago; it can be aerosolised, or used to contaminate food,8 and the estimated lethal oral dose is 70 µg. The Aum Shinrikyo cult released aerosolised toxin in Japan in the 1990s, but fortunately no cases of botulism resulted. The Soviet Union and Iraq have produced large amounts of botulinum toxin, and Iraq loaded toxin into missiles and bombs.8 Clinical featuresTwo forms of botulism could arise from deliberate release of botulinum toxin — foodborne and inhalational botulism. In contrast, gastrointestinal (infant) and wound botulism arise from infection with C. botulinum, rather than ingestion or inhalation of toxin, and are unlikely to occur in a biological attack. Foodborne botulism, the most common natural form of the disease, results from ingestion of preformed toxin that is produced when food contaminated with C. botulinum has been stored under anaerobic conditions. Cases are mostly associated with improperly home-bottled or preserved foods, but could potentially result from intentional addition of toxin to food. Botulism after inhalation of aerosolised toxin is an unnatural, man-made form of the disease, and would be the intended result of toxin delivery by missiles, bombs or aerosolisation devices. Only one instance of inhalational botulism has been reported, involving accidental exposure of three veterinary personnel to toxin re-aerosolised from animal fur.8 The incubation period for gastrointestinal botulism and probably also inhalational botulism (based on animal studies) is usually 12 to 72 hours. All forms of botulism have identical clinical features, with the exception that foodborne botulism may be preceded by gastrointestinal symptoms (nausea, vomiting, diarrhoea, abdominal cramps).8 The pattern of illness is characteristic: onset with cranial nerve palsies of bulbar distribution, followed by descending motor weakness (from head and chest muscles to upper, then lower, limbs) in a patient with a normal conscious state and no fever.9 Absence of sensory changes is another important negative feature. Reflexes are preserved early, but may be lost with time. Dilated pupils, blurred vision, dry mouth and constipation indicate parasympathetic involvement. Severity of the weakness and its rate of progression vary, depending on the amount of toxin ingested. With modern medical therapy, mortality of foodborne botulism is less than 10%. DiagnosisDiagnosis is initially clinical. The principal differential diagnoses are the Miller–Fisher variant of Guillain–Barré syndrome (a demyelinating condition causing cranial nerve palsies and absent deep tendon reflexes) and disorders of the neuromuscular junction, such as myasthenia gravis. These and other conditions can be differentiated from botulism on the basis of clinical signs (eg, impaired consciousness in brainstem stroke or infection), analysis of the cerebrospinal fluid (infection and Guillain–Barré syndrome), neuroimaging (stroke) and electromyography (myasthenia gravis). Laboratory testing for botulism is complicated and time consuming and is available only through selected public health laboratories. To detect toxin, mice are inoculated with serum, faeces or vomitus; the organism, if present, can also be cultured from these specimens. Results are not available soon enough to assist initial diagnosis or management. Management and preventionPrompt administration of botulinum antitoxin, available in the US but not Australia, lessens disease severity. As the toxin is an equine preparation, serum-sickness-like reactions may occur in some recipients, but anaphylaxis is rare. Otherwise, treatment is supportive. Close respiratory monitoring is essential, and patients should be admitted to an intensive care or high-dependency unit. In one foodborne outbreak, 20% of patients required mechanical ventilation. An investigational toxoid vaccine has been given to laboratory and military personnel in the United States but is not available for more widespread use. 1: Smallpox lesions in an unvaccinated child Evolution of smallpox lesions from papules (top left; three days after onset of fever) to vesicles and pustules (bottom right; nine days after onset of fever). For the first two to three days, the rash of smallpox resembles that of chickenpox, but the two can be differentiated by the following: Smallpox lesions appear after two to three days of prominent prodromal symptoms (fever, headache and backache) and develop slowly (over nine to 10 days). Chickenpox lesions develop rapidly after a one- to two-day prodrome (fever and malaise). All smallpox lesions develop at the same pace and, on any part of the body, appear identical. Chickenpox lesions are much more superficial and develop in crops over a two- to four-day period, with scabs, vesicles and pustules seen simultaneously on adjacent areas of skin. Smallpox lesions are most concentrated on the face, arms and legs, and may occur on the palms or soles. Chickenpox lesions are most dense over the trunk and almost never found on the palms or soles. 2: Clostridium botulinum Gram-positive rods with characteristic subterminal spores (Gram stain; original magnification x 1000). (Picture courtesy Microbiological Diagnostic Unit, Public Health Laboratory, University of Melbourne, VIC.)

Michael Whitby FRACP, FRCPA · Alan C Street FRACP · Tilman A Ruff FRACP · Frank Fenner MD, FRS