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The accessory subunit of mitochondrial DNA polymerase gamma, POLGbeta, functions as a processivity factor in vitro. Here we show POLGbeta has additional roles in mitochondrial DNA metabolism. Mitochondrial DNA is arranged in nucleoprotein complexes, or nucleoids, which often contain multiple copies of the mitochondrial genome. Gene-silencing of POLGbeta increased nucleoid numbers, whereas over-expression of POLGbeta reduced the number and increased the size of mitochondrial nucleoids. Both increased and decreased expression of POLGbeta altered nucleoid structure and precipitated a marked decrease in 7S DNA molecules, which form short displacement-loops on mitochondrial DNA. Recombinant POLGbeta preferentially bound to plasmids with a short displacement-loop, in contrast to POLGalpha. These findings support the view that the mitochondrial D-loop acts as a protein recruitment centre, and suggest POLGbeta is a key factor in the organization of mitochondrial DNA in multigenomic nucleoprotein complexes.

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The prototype of the chain saw familiar today in the timber industry was pioneered in the late 18th Century by two Scottish docors, John Aitken and James Jeffray, for symphysiotomy and excision of diseased bone respectively. The chain hand saw, a fine serrated link chain which cut on the concave side, was invented around 1783-1785. It was illustrated in Aitken's Principles of Midwifery or Puerperal Medicine (1785) and used by him in his dissecting room. Jeffray claimed to have conceived the idea of the chain saw independently about that time but it was 1790 before he was able to have it produced. In 1806, Jeffray published Cases of the Excision of Carious Joints by H. Park and P. F. Moreau with Observations by James Jeffray M.D.. In this communication he translated Moreau's paper of 1803. Park andMoreau described successful excision of diseased joints, particularly the knee and elbow. Jeffray explained that the chain saw would allow a smaller wound and protect the adjacent neurovascular bundle. While a heroic concept, symphysiotomy had too many complications for most obstetricians but Jeffray's ideas became accepted, especially after the development of anaesthetics. Mechanised versions of the chain saw were developed but in the later 19th Century, it was superseded in surgey by the Gigli twisted wire saw. For much of the 19th Century, however, the chain saw was a useful surgical instrument.

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Using molecular methods the authors have studied mycobacterial DNA taken from a 19th century victim of tuberculosis. This was the case from which Robert Koch first isolated and cultured the organism responsible for tuberculosis. The mycobacteria were preserved within five glass culture tubes as abundant bacterial colonies on slopes of a gelatinous culture medium of unknown composition. Originally presented by Koch to surgical laryngologist Walter Jobson Horne in London in 1901, the relic has, since 1983, been in the care of the Royal College of Surgeons of England. Light and electron microscopy established the presence of acid-fast mycobacteria but showed that morphological preservation was generally poor. Eleven different genomic loci were successfully amplified by PCR. This series of experiments confirmed that the organisms were indeed Mycobacterium tuberculosis and further showed that the original strain was in evolutionary terms similar to 'modern' isolates, having undergone the TB D1 deletion. Attempts to determine the genotypic group of the isolate were only partially successful, due in part to the degraded nature of the DNA and possibly also to a truncation in the katG gene, which formed part of the classification scheme. Spoligotyping resulted in amplification of DR spacers consistent with M. tuberculosis but with discrepancies between independent extracts, stressing the limitations of this typing method when applied to poorly preserved material.

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Instruments manufactured by bending a basic metal strip or rod, either about its middle to create spring forceps (tweezers), or towards one extremity to create hooks and retractors are related structures. Spring forceps depend on tension mediated at the bend (hoop) or fixed end which is transmitted as dynamic 'spring' to the jaws, whereas the bend of hooks and retractors remains fixed and static. If such instruments refine the digital postures of pinch, pincer and retraction during surgery, they have not supplanted these manual actions entirely. After a brief historical introduction, the structure, modifications, functions and controls of spring forceps are analysed. Importantly, this instrument enjoys both right and left-handed functions, some of which are ancient, some transient as haemostats and needle-holders, and some, including left-handed dissection, surprisingly recent. Hooks are sharp or blunt and, among other functions, pre-date the left-handed spring forceps for dissection; in general hooks function as retractors. Hand-held retractors are enlarged blunt hooks, the wide retracting contact surface reducing trauma to wound margins and viscera. The physical effort of employing these retractors deep in body cavities is abated by applying them autostatically around a square or circular frame.

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Woodall's remark on limb amputation, in 1617, that "it is no small presumption to Dismember the Image of God", reflected lingering doubts attributable to widespread ancient beliefs or taboos which, at least during the early historic period, shunned elective amputations completely. Death was preferred to operative destruction of the body's integrity, even when societies were aware of traumatic, disease-induced and legal amputations, eventually to be accepted and managed rationally. Deep-rooted resistance to planned dismemberment became unbalanced by the malevolent wounds of gunshot missiles which contrasted vividly with cold steel and blunt injuries of earlier warfare. Massive soft tissue destruction, bone comminution and, above all, embedded missiles and clothing posed perplexing complications for both patients and surgeons, often causing gangrene and death. Finally despite resultant deformity, amputation was recognised as a means of preserving life. It is maintained the philosophical perception, believing it is better to live with three limbs than to die with four, gained acceptance due to the persuasive influence of gunpowder on battlefields and in battle-ships. Notwithstanding, until carbolised catgut ligatures were employed amputation remained a hazardous procedurep it persists as a repugnant operation of last resort.

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Elective surgery requires planned incisions and incisions require appropriate blades. In the prehistoric era, division of the umbilical cord and other minor procedures were probably undertaken with human teeth and nails, and later with plant, animal and mineral substitutes, as witnessed by studies of primitive societies still surviving or recently extinct. More efficient metallic blades appeared in historic times and ultimately generated five specific shapes which are analysed in detail. Today, as minimally invasive techniques, endoscopes, laser and ultrasound sources evolve, many hallowed incisions of surgical access diminish in length or disappear entirely. In historical terms, elective surgery of the twentieth century will be recalled as an interlude characterised by maximally invasive incisions.

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Whereas John Hunter (1728-93) the anatomist, zoologist, physiologist, pathologist and museum collector receives unceasing eulogy, his work as a practising surgeon is curiously neglected. As far as can be determined, there are no studies devoted to his instruments and operative technique before a personal investigation in 1991, perhaps for the good reason that these would prove inconclusive. Nevertheless, the writer believes sufficient evidence is available to justify further communication.

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The publication of "Orthopédie" by Andry in 1741 promoted a comprehensive approach to children's deformities, introducing both a new word and a twisted tree emblem, which now delineate a modern speciality. A brief appreciation of Andry's book and stormy career focusses on the limitations of his work, which was written for parents. The etymological constraints of orthopaedy are noted, its suggested rivals discussed and the unsatisfactory adaptations of the word in English high-lighted. "Orthopaedics", a deformed adjective used as a noun, and "pediatric orthopaedics" are defective absurdities which could be remedied by a new, accurate and all-embracing noun "orthosurgery".

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Man's failure to extract deeply embedded thorns and arrowheads, with bare hands and teeth, stimulated 'instrument substitutes' mimicking these appendages. Evidence from primitive communities suggest animal, plant and mineral items were employed, both before and after metal became the standard material of today's armamentarium. Changing surgical instrument composition has mirrored concurrent technology and manufacturing methods both of which are reviewed. Particular significance is accorded flint, bronze, crucible steel, thermal sterilisation, nickel-plate, stainless steel and disposable plastics. The paper is based on an exhibition From Flint to Stainless Steel on display at the College.

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