Solving an infectious problem

Deaths from infection by hospital superbugs continue to make news headlines with hospital-acquired infections, though often responding to antibiotics, killing around 5000 people in the UK each year.¹  However, such mortality is not new and was, relatively speaking, even more of a problem 150 years ago. Then, operations were relatively rare with even large city hospitals only averaging two or three per week. While the pain of surgery without anaesthetic was a major disincentive, there was also a high risk of death from infection. In 1869 obstetrician James Young Simpson examined the outcome of amputations, the most common operation at the time. While 43 per cent of the 2000 patients treated in big hospitals died, this figure fell to only 13 per cent for those operated on in small hospitals or at home. Clearly there was something lethal about large hospitals.  

Lethal infections

Once infections were established, they could cause gangrene, or spread skin infection (erysipelas) or septicaemia with abscesses (pyaemia). Frequently, the body's defences would be overwhelmed and patients would die. One proposed cause of infection was miasma - the smell from drains and other patients' wounds, presumed to be transmitted by air. If air could be excluded using various plasters and dressings, this might prevent infection.  

When Joseph Priestley discovered oxygen in 1775, this new gaseous chemical was believed by some scientists and physicians to be the cause of infections and more wound dressings were applied to stop this potential threat. In contrast, carbon dioxide (CO₂) was thought to be beneficial to healing and various contraptions were used to surround wounds with CO₂. In the first half of the 19^th century, at least in some hospitals, the methods used to exclude air were thought to make the infections worse. So dressings were removed and wounds were irrigated with water, and covered with cloths to keep flies off. But this didn't work either. The outlook was particularly bleak for patients with compound fractures, where broken bones poke through the skin. Splints were useless; the skin wounds became infected and death was almost inevitable. The recommended treatment was amputation, notwithstanding a mortality rate of around 50 per cent.  

Enter Joseph Lister

Joseph Lister, a surgeon working in Glasgow, wondered if anything could be done to lessen the risk of infection. In his first paper on this topic in March 1867 he mentions the work of Louis Pasteur, which was published in the early 1860s:  

However, Lister doesn't credit Pasteur, but mentions the miasmatic infection theory as inspiring his work: 

Lister went on to describe numerous successful operations to repair compound fractures, in which phenol (1) played a prominent part in cleansing wounds, sterilising both the instruments and the surgeon's hands, and in post-operative dressings. This heralded the era of antiseptic surgery. But this approach was not universally accepted and both Lister and his methods were attacked. There were two strands of criticism. One allegation was that using phenol was nothing special, and Lister's success rate could be matched elsewhere without using either phenol or other antiseptics. The second, vitriolic and personal criticism, led by James Young Simpson³  was that the technique was not new. Phenol had been used for years, mainly in France, to treat seeping wounds and to minimise the risk of infection occurring in the first place.  

But what provoked Simpson? At the time he had his own technique for reducing wound infections called acupressure. He threaded steel needles, rather than cotton sutures (stitches), several times through the ends of severed arteries to stop bleeding. This was a less favourable environment for infections to take hold than bloodstained cotton. However, Simpson's discovery was immediately eclipsed by Lister and his use of phenol in antiseptic surgery. Ironically, Simpson had used a phenolic mixture, called 'McDougall's powder',* in his obstetric practice in 1860 and if he had persevered he might have anticipated Lister's discovery. Perhaps this drove his attacks on Lister. But what grounds are there for Simpson's claim that Lister's method was not new? 

Early Antisepsis

The term 'antiseptic' was coined in 1750 by a military surgeon, Sir John Pringle, formerly professor of moral philosophy at the University of Edinburgh. He investigated the preservative properties of various salts (antiseptics) on beef, and other substances to disinfect wounds. He found that a suspension of bleaching powder, known as 'chloride of lime', was the most effective.  

Almost a century later, in 1847, the Hungarian physician Ignaz Semmelweis proposed that it was doctors returning to delivery rooms from autopsies on women who had died from 'childbed fever' that were responsible for the high rate of this often fatal condition in large hospitals. Death rates were reduced by 40 per cent when doctors washed their hands in chloride of lime. Despite this, Semmelweis's suggestion that doctors themselves caused mothers' deaths was so threatening that he was ostracised and eventually committed to an asylum. Lister didn't know about Semmelweis's work, which predated Pasteur's. 

Phenol and the French connection

What about Lister's use of phenol in antiseptic surgery? When heated in the absence of air coal produces three products: a gas (used in street and home lighting from ca  1810); coke (used as both a fuel and as a reducing agent in the manufacture of iron); and a black, smelly, viscous liquid called coal tar. At the start of the 19th century this byproduct was normally discarded, though some coal tar was used in preserving wood. However, over the next decades coal tar was increasingly used as a source of organic chemicals. Its phenol content could be as high as 3 per cent and in 1834 German chemist Friedlieb Runge isolated this chemical component, which he called carbolic acid because of its acidic properties. Almost 10 years later in 1842 the French chemist Charles Gerhardt spotted the chemical's connection with benzene-derived compounds and named it phenol.  

Runge found that phenol had a preservative effect on what he called unspecified 'animal matters', but it was too expensive to use on a large scale. However, the coal tar precursor was very cheap and in 1844 a French physician, Henri-Louis Bayard, absorbed coal tar on a clay base and used the resulting powder to disinfect sewage. In 1859 the French physician Edmond Corne, assisted by a Dr Demeaux, used a similar mixture, substituting plaster of Paris for the clay. Two years later The Lancet  reported: '[it] cleansed offensive wounds and fetid ulcerations, diminished the chances of purulent infection, and accelerated the healing process'.⁴  One problem was that the mixture tended to set solid around wounds, preventing them from draining, which at the time was thought to be essential for healing. The early demise of the manufacturing company suggests that the coal tar mixture did not live up to its initial promise.  

In 1863 another Frenchman, Jules Lemaire, reported that he saw a reduction in post-surgical infections when both coal tar and phenol were used to treat the wounds, predating Lister's studies by four years. His story begins in 1850 with the work of Ferdinand Le Boeuf, a pharmacist working in Bayonne. He was investigating the properties of saponin, an extract from the bark of a South American tree, Quillaja saponaria. Used as a soap substitute in its native Panama, Le Boeuf reported: 

Le Boeuf extended his investigation by applying the same techniques to converting sticky coal tar into a milky fluid. He was aware that coal tar was used for dressing wounds, and wondered if his emulsion might be a more convenient alternative. For help, he turned to Lemaire, who was both a physician and a pharmacist. In 1859 Lemaire treated a patient suffering from a large gangrenous wound in the cleft of the buttocks with Le Boeuf's coal tar emulsion.⁵  The result was spectacular. The discharge stopped, the infection cleared up and the wound healed. In their report Lemaire remarked on 'all the advantages that surgery would enjoy from this preparation'. He began to investigate the tar's numerous components and found that phenol was responsible for its disinfecting/curative properties. With this discovery he gradually shifted the focus of his investigations to 'l'acide phénique'.⁶ 

Lister and the forgotten pioneers

Generally, Lemaire and his followers used their preparations after surgery to stop infections developing, or to deal with infections once they had developed. Around the same time F. Crace Calvert, professor of chemistry at the Royal Manchester Institution, was also promoting phenol as an antiseptic. Calvert was responsible for the first commercial production of phenol and supplied the sewage works in Carlisle that first piqued Lister's interest and later supplied Lister himself. In 1851 he had injected cadavers with phenol solutions, which prevented them deteriorating for three to four weeks, and before 1865 had supplied several Manchester surgeons with phenol for therapeutic trials. But these names are almost unknown compared to Lister. 

Lister's great contribution to medicine was two-fold. First, he used phenol before the first incision was made. The patient's skin, surgical instruments, sutures and the surgeon's hands were all washed or steeped in phenol. Pasteur had found that the infective agents were bacteria-contaminated dust particles in the air and Lister also devised a spray to 'sterilise the air' around the operation but he stopped using this around 1887 because it offered little benefit. Lister must get credit for pioneering antiseptic surgery - even though others can claim that they used post-surgical antiseptics earlier. More importantly, he recognised the key principle underlying this change in surgical practice, and converted a chance observation into a meaningful application of the scientific principles proposed by Pasteur.  

Clearly others, not just in France, were experimenting with coal tar and phenol as a way of reducing post-operative infections before Lister published his work. Although Lemaire was pre-eminent amongst these, today his contributions are all but forgotten. Even his countrymen attach no particular significance to his name.⁷  Why then is Lemaire's contribution neglected?  

There are three important criteria that need to be looked at when considering whether someone should be credited with making a scientific discovery: 

• the person must make the discovery; 
• the discoverer must understand its significance in the context of the prevailing knowledge; 
• they must also alert the world to the discovery. 

Lemaire was a general practitioner working alone, and though he published his findings in a book, this had a limited circulation. His extravagant claims for phenol - ie  it could cure acne, asthma, cholera, dysentery, tuberculosis, smallpox and much more - may have put off sceptical readers. In contrast, Lister worked in hospitals with many assistants eager to tell people about his work, he could obtain data from large numbers of patients, and he published in leading journals such as The Lancet.  

Perhaps Lister was fortunate to benefit from particular circumstances and that the conditions were ripe for developing antiseptic surgery. However, while discoveries and conclusions are easy with hindsight, the failure of others such as Semmelweis, Lemaire and even Calvert to capitalise on their insights, to communicate effectively and to persist (or be allowed to persist) in the face of vigorous opposition only serve to show the brilliance of Lister as a scientist.  

Alan Dronsfield is emeritus professor of the history of science in the school of education, health and sciences at the University of Derby, Derby DE22 1GB. Peter Ellis is professor of psychological medicine at the school of medicine and health sciences, University of Otago, Wellington, PO Box 7343, Wellington South, New Zealand. 

Further Reading

There have been three attempts to gain greater recognition for Lemaire as one of the pioneers of antisepsis.^{5, 8, 9}  For accounts of the history of antisepsis, both before and after Lister, see the works by Cheyne, Wangensteen and Gaw.¹⁰