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Joseph Lister
19th and 20th-century British surgeon and antiseptic pioneer

Joseph Lister, 1st Baron Lister, OM, PC, FRS, FRCSE, FRCPGlas, and FRCS (1827–1912), was a British surgeon and pioneer of antiseptic surgery and preventive healthcare. At the Glasgow Royal Infirmary, he introduced carbolic acid (phenol) as a steriliser, dramatically reducing post-operative infections. Lister’s research on bacteriology, infection, and wound inflammation supported Louis Pasteur’s germ theory, revolutionizing the craft of surgery and earning him the title “father of modern surgery.”

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Early life

Lister was born to a prosperous, educated Quaker family in the village of Upton, then near but now in London,10 England. He was the fourth child and second son of four sons and three daughters11 born to gentleman scientist and wine merchant Joseph Jackson Lister and school assistant Isabella Lister née Harris.1213 The couple married in a ceremony held in Ackworth, West Yorkshire on 14 July 1818.14

Lister's paternal great-great-grandfather, Thomas Lister was the last of several generations of farmers who lived in Bingley in West Yorkshire.15 Lister joined the Society of Friends as a young man and passed his beliefs on to his son, Joseph Lister.16 He moved to London in 1720 to open a tobacconist's shop17 in Aldersgate Street in the City of London.18 His son, John Lister, was born there. Lister's grandfather was apprenticed to watchmaker Isaac Rogers,19 in 1752 and followed that trade on his own account in Bell Alley, Lombard Street from 1759 to 1766. He then took over his father's tobacco business,20 but gave it up in 1769 in favour of working at his father-in-law Stephen Jackson's business as a wine-merchant at No 28 Old Wine and Brandy Values on Lothbury Street, opposite Tokenhouse Yard.21

His father was a pioneer in the design of achromatic object lenses for use in compound microscopes22 He spent 30 years perfecting the microscope, and in the process, discovered the Law of Aplanatic Foci,23 building a microscope where the image point of one lens coincided with the focal point of another.24 Up until that time, the best higher magnification lenses produced an excessive secondary aberration known as a coma, which interfered with normal use.25 It was considered a major advance that elevated histology into an independent science.26 By 1832, Lister's work had built a reputation sufficient to enable his being elected to the Royal Society.2728 His mother, Isabella, was the youngest daughter of master mariner Anthony Harris.29 Isabella worked at the Ackworth School, a Quaker school for the poor, assisting her widowed mother, the superintendent of the school.30

ParentsIsabella Harris c. 1839Joseph Jackson Lister

The eldest daughter of the couple was Mary Lister. On 21 August 1851, she married the barrister Rickman Godlee31 of Lincoln's Inn and the Middle Temple, who belonged to the Friends meeting house in Plaistow.32 The couple had six children. Their second child was Rickman Godlee, a neurosurgeon who became Professor of Clinical Surgery at the University College Hospital33 and surgeon to Queen Victoria. He became Lister's biographer in 1917.34 The eldest son of Joseph and Isabella Lister was John Lister, who died of a painful brain tumour.35 With John's death, Joseph became the heir of the family.36 The couple's second daughter was Isabella Sophia Lister, who married Irish Quaker Thomas Pim37 in 1848. Lister's other brother William Henry Lister died after a long illness.38 The youngest son was Arthur Lister, a wine merchant, botanist and lifelong Quaker, who studied Mycetozoa. He worked alongside his daughter Gulielma Lister to produce the standard monograph on Mycetozoa. By 1898, Lister's work had built a reputation sufficient to enable his election to the Royal Society.39 Gulielma Lister, a talented artist, later updated the standard monograph with colour drawings. Her work built a reputation sufficient to be elected a fellow of the Linnean Society in 1904. She becoming its vice-president in 1929.40 The couple's last child was Jane Lister; she married widower Smith Harrison, a wholesale tea merchant.41

After their marriage, the Listers lived at 5 Tokenhouse Yard in Central London for three years until 1822, where they ran a port wine business in partnership with Thomas Barton Beck.42 Beck was the grandfather of the professor of surgery and proponent of the germ theory of disease, Marcus Beck,43 who would later promote Lister's discoveries in his fight to introduce antiseptics.44 In 1822, Lister's family moved to Stoke Newington.45 In 1826, the family moved to Upton House, a long low Queen Anne style mansion46 that came with 69 acres of land.47 It had been rebuilt in 1731, to suit the style of the period.48

Early homesUpton House. The watercolour was created by his older sister, Mary Joseph.

Education

School

As a child, Lister had a stammer and this was possibly why he was educated at home until he was eleven.49 Lister then attended Isaac Brown and Benjamin Abbott's Academy, a private50 Quaker school in Hitchin, Hertfordshire.51 When Lister was thirteen,52 he attended Grove House School in Tottenham, also a private Quaker School53 to study mathematics, natural science, and languages. His father was insistent that Lister received a good grounding in French and German, in the knowledge he would learn Latin at school.54 From an early age, Lister was strongly encouraged by his father55 and would talk about his father's great influence later in life, particularly in encouraging him in his study of natural history.56 Lister's interest in natural history led him to study bones and to collect and dissect small animals and fish that were examined using his father's microscope57 and then drawn using the camera lucida technique that his father had explained to him,58 or sketched.59 His father's interests in microscopical research developed in Lister the determination to become a surgeon60 and prepared him for a life of scientific research.61 None of Lister's relatives were in the medical profession. According to Godlee, the decision to become a physician seemed to be an entirely spontaneous decision.62

In 1843 his father decided to send him to university. As Lister was unable to attend either University of Oxford or the University of Cambridge owing to the religious tests that effectively barred him,63 he decided to apply to the non-sectarian University College London Medical School (UCL), one of only a few institutions in Great Britain that accepted Quakers at that time.64 Lister took the public examination in the junior class of botany, a required course that would enable him to matriculate.65 Lister left school in the spring of 1844 when he was seventeen.66

Schools that Lister attendedThe Lord Lister Hotel in Hitchin, formerly Isaac Brown and Benjamin Abbott's Academy, where Lister was a student from 1838 to 1841Grove House, a private Quaker school in Tottenham. A lithograph by W.D. Sparkes in 1842.

University

In 1844, just before Lister's seventeenth birthday, he moved to an apartment at 28 London Road that he shared with Edward Palmer, also a Quaker.67 Between 1844 and 1845, Lister continued his pre-matriculation studies, in Greek, Latin and natural philosophy.68 In the Latin and Greek classes, he won a "Certificate of Honour".69 For the experimental natural philosophy class, Lister won first prize and was awarded a copy of Charles Hutton's "Recreations in Mathematics and Natural Philosophy".70

Although his father wanted him to continue his general education,71 the university had demanded since 1837, that each student obtain a Bachelor of Arts (BA) degree before commencing medical training.72 Lister matriculated in August 1845, initially studying for a BA in classics.73 Between 1845 and 1846, Lister studied the mathematics of natural philosophy, mathematics and Greek earning a "Certificate of Honour" in each class.74 Between 1846 and 1847, Lister studied both anatomy and atomic theory (chemistry) and won a prize for his essay.75 On 21 December 1846, Lister and Palmer attended Robert Liston's famous operation where ether was applied by Lister's classmate, William Squire to anaesthetise a patient for the first time.7677 On 23 December 1847, Lister and Palmer moved to 2 Bedford Place and were joined by John Hodgkin, the nephew of Thomas Hodgkin who discovered Hodgkin lymphoma.78 Lister and Hodgkin had been school friends.79

In December 1847, Lister graduated with a degree of Bachelor of Arts 1st division, with a distinction in classics and botany.80 While he was studying, Lister suffered from a mild bout of smallpox, a year after his elder brother died of the disease.81 The bereavement combined with the stress of his classes led to a nervous breakdown in March 1848.82 Lister's nephew Godlee used the term to describe the situation and is perhaps indicative that adolescence was just as difficult in 1847, as it is now.83 Lister decided to take a long holiday84 to recuperate and this delayed the start of his studies.85 In late April 1848, Lister visited the Isle of Man with Hodgkin and by 7 June 1848, he was visiting Ilfracombe.86 At the end of June, Lister accepted an invitation to stay in the home of Thoman Pim, a Dublin Quaker. Using it as his base, Lister travelled throughout Ireland.87 On 1 July 1848, Lister received a letter full of warmth and love from his father where his last meeting was "...sunshine after a refreshing shower, following a time of cloud" and advised him to "cherish a pious cheerful spirit, open to see and to enjoy the bounties and the beauties spread around us :—not to give way to turning thy thoughts upon thyself nor even at present to dwell long on serious things".88 From 22 July 1848, for more than a year, the record is blank.89

Medical student

Lister registered as a medical student in the winter of 184990 and became active in the University Debating Society and the Hospital Medical Society.91 In the autumn of 1849, he returned to college with a microscope given to him by his father.92 After completing courses in anatomy, physiology and surgery, he was awarded a "Certificate of Honours", winning the silver medal in anatomy and physiology and a gold medal in botany.93

His main lecturers were John Lindley professor of botany, Thomas Graham professor of chemistry, Robert Edmond Grant professor of comparative anatomy, George Viner Ellis professor of anatomy and William Benjamin Carpenter professor of medical jurisprudence.94 Lister often spoke highly of Lindley and Graham in his writings, but Wharton Jones professor of ophthalmic medicine and surgery, and William Sharpey professor of physiology, exercised the greatest influence on him.95 He was greatly attracted by Dr. Sharpey's lectures, which inspired in him a love of experimental physiology and histology that never left him.96

Thomas Henry Huxley praised Wharton Jones for the method and quality of his physiology lectures.97 As a clinical scientist working in physiological sciences, he was foremost in the number of discoveries he made.98 He was also considered a brilliant ophthalmic surgeon, his main field.99 He conducted research into the circulation of blood and the phenomena of inflammation, carried out on the frog's web100 and the bat's wing, and no doubt suggested this method of research to Lister.101 Sharpey was called the father of modern physiology as he was the first to give a series of lectures on the subject.102 Prior to that the field had been considered part of anatomy.103 Sharpey studied at Edinburgh University, then went to Paris to study clinical surgery under French anatomist Guillaume Dupuytren and operative surgery under Jacques Lisfranc de St. Martin. Sharpey met Syme while in Paris and became the two became life-long friends.104 After he moved to Edinburgh he taught anatomy with Allen Thomson as his physiological colleague. He left Edinburgh in 1836, to become the first Professor of Physiology.

Lister's university and his lecturersGower street entrance to the universityWharton JonesWilliam SharpeyJohn LindleyThomas GrahamRobert GrantWilliam Carpenter

Clinical instruction

To qualify for his degree, Lister had to complete two years of clinical instruction,105 and began his residency at University College Hospital in October 1850.106 as an intern and then house physician to Walter Hayle Walshe,107 professor of pathological anatomy and author of the 1846 study, The Nature and Treatment of Cancer.108 Lister in 1850 again received "Certificates of Honours" and won two gold medals in anatomy and a silver medal each in surgery and medicine.109

In his second year in 1851, Lister became first a dresser in January 1851110 then a house surgeon to John Eric Erichsen in May 1851.111 Erichsen was professor of surgery112 and author of the 1853 Science and Art of Surgery,113 described as one of the most celebrated English-language textbooks on surgery.114 The book went through many editions; Marcus Beck edited the eighth and ninth, adding Lister's antiseptic techniques and Pasteur and Robert Koch's germ theory.115

Lister's first case notes were recorded on 5 February 1851. As a dresser, his immediate superior was Henry Thompson, who recalled "..a shy Quaker...I remember that he had a better microscope than any man in the college".116

Lister had only just begun working in his role as dresser to Erichsen in January 1851, when an epidemic of erysipelas broke out in the male ward.117 An infected patient from an Islington workhouse was left in Erichsen's surgical ward for two hours.118 The hospital had been free of infection but within days there were twelve cases of infection and four deaths.119 In his notebook, Lister stated that the disease was a form of surgical fever, and particularly noted that recent surgical patients were infected the worst, but that those with older surgeries with suppurating wounds, 'mostly escaped'.120 It was while Lister worked for Erichsen, that his interest in the healing of wounds began.121 Erichsen was a miasmatist who thought the wounds became infected from miasmas from the wound itself that caused a noxious form of "bad air" that spread to other patients in the ward.122 Erichsen believed that seven patients with an infected wound had saturated of the ward with "bad air", which spread to cause gangrene.123 However Lister saw that some wounds, when debrided and cleaned, would sometimes heal. He believed that something in the wound itself was at fault.124

When he became a house surgeon, Lister had patients put in his charge.125 For the first time, he came into contact face-to-face with various forms of blood-poisoning diseases like pyaemia126 and hospital gangrene, which rots living tissue with a remarkable rapidity.127128 While examining in an autopsy an excision of the elbow of a little boy who had died of pyaemia, Lister noticed that a thick yellow-pus was present at the seat of the humerus bone, and distended the brachial and axillary veins.129 He also noticed that the pus advanced in the reverse direction along the veins, bypassing the valves in the veins.130 He also found suppuration in a knee-joint and multiple abscesses in the lungs.131 Lister knew that Charles-Emmanuel Sédillot had discovered that multiple abscesses in the lungs were caused by introducing pus into the veins of an animal. At the time he could not explain the facts but believed the pus in the organs had a metastatic origin.132 On 2 October 1900, during The Huxley Lecture, Lister described how his interest in the germ theory of disease and how it applied to surgery began with his investigation into the death of that little boy.133

There was an epidemic of gangrene during his surgeoncy. The treatment method was to chloroform the patient, scrape the soft slough off and burn the necrotic flesh away with mercury pernitrate134 Occasionally the treatment would succeed, but when a grey film appeared at the edges of the wound, it presaged death.135 In one patient, the repeated treatment failed several times, so Erichsen amputated the limb, which healed fine.136 Lister recognised was that the disease was a "local poison" and probably parasitic in nature.137 He examined the diseased tissues under his microscope. He saw peculiar objects that he could not identify, as he had no frame of reference to draw conclusions from these observations.138 In his notebook he recorded:

I imagined they might be the materies morbi in the form of some kind of fungus.139

Lister wrote two papers on the epidemics; but both were lost: Hospital gangrene140 and Microscope. They were read to the Student Medical Society at UCL.141

Lister's first operation

On 26 June 2013, medical historian Ruth Richardson and orthopaedic surgeon Bryan Rhodes published a paper in which they described their discovery of Lister's first operation, made while both were researching his career.142 At 1 pm on 27 June 1851, Lister, a second-year medical student working at a casualty ward in Gower Street, conducted his first operation. Julia Sullivan, a mother of eight grown children, had been stabbed in the abdomen by her husband, a drunk and ne'er-do-well, who was taken into custody.143 On 15 September 1851, Lister was called as a witness to the husband's trial at the Old Bailey.144 His testimony helped convict the husband, who was transported to Australia for 20 years.145

About a yard of small intestine about eight inches across, damaged in two places, protruded from the woman's lower abdomen, which had three open wounds.146 After cleaning the intestines with blood-warm water, Lister was unable to place them back into the body, so he decided to extend the cut.147 then placed them back into the abdomen, and sewed and sutured the wounds shut.148 He administered opium to induce constipation and enable the intestines to recover. Sullivan recovered her health.149 This was a full decade before his first public operation in the Glasgow Infirmary.150

This operation was missed by historians.151 Liverpool consultant surgeon John Shepherd, in his essay on Lister, Joseph Lister and abdominal surgery, written in 1968,152 failed to mention the operation, and instead started his account from the 1860s onwards. He apparently was unaware of this surgery.153

Microscope experiments 1852

Observations on the Contractile Tissue of the Iris

Lister's first paper,154 written while he was still at university,155 was published in the Quarterly Journal of Microscopical Science in 1853.156

On 11 August 1852, Lister attended an operation at University College Hospital by Wharton Jones,157 who presented him with a fresh slice of human iris. Lister took the opportunity to study the iris.158 He reviewed existing research and studied tissue from a horse, a cat, a rabbit and a guinea pig as well as six surgical specimens from patients who had undergone eye surgery.159 Lister was unable to complete his research to his satisfaction, due to his need to pass his final examination. He offered an apology in the paper:

My engagements do not allow me to carry the inquiry further at present; and my apology for offering the results of an incomplete investigation is that a contribution tending, in however small a degree, to extend our acquaintance with so important an organ as the eye, or to verify observations that may be thought doubtful, may probably be of interest to the physiologist.160

The paper advanced the work of Swiss physiologist Albert von Kölliker, demonstrating the existence of two distinct muscles, the dilator and sphincter in the iris.161 This corrected the convictions of previous researchers that there was no dilator pupillae muscle.162

Observations on the Muscular Tissue of the Skin

His next paper, an investigation into goose bumps,163164 was published on 1 June 1853 in the same journal.165 Lister was able to confirm Kölliker's experimental finding that in humans the smooth muscle fibres are responsible for making hair stand out from the skin, in contrast to other mammals, whose large tactile hairs are associated with striated muscle.166 Lister also demonstrated a new method of creating histological sections from the tissue of the scalp.167

Lister's microscopy skills were so advanced that he was able to correct the observations of German histologist Friedrich Gustav Henle, who mistook small blood vessels for muscle fibres.168 In each of the papers, he created camera lucida drawings so accurate that they could be used to scale and measure the observations.169

Both papers attracted significant attention in Britain and abroad.170 Naturalist Richard Owen, an old friend of Lister's father, was particularly impressed by them.171 Owen contemplated recruiting Lister for his department and forwarded him a thank-you letter on 2 August 1853.172 Kölliker was particularly pleased with the analysis that Lister had formulated. Kölliker made many trips to Britain, and eventually met Lister. They became life-long friends.173 Their close friendship was described in a letter by Kölliker on 17 November 1897, that Rickman Godlee chose to use to illustrate their relationship.174 Kölliker sent a letter to Lister when he was president of the Royal Society, congratulating him on receiving the Copley medal, fondly remembering old friends who had died, and celebrating his time in Scotland with Syme and Lister. Kölliker was 80 years old at the time.175

Graduation

Lister graduated with a Bachelor of Medicine with honours in the autumn of 1852.176 During his final year, Lister won several prestigious awards heavily contested among the student body of London teaching hospitals.177 He won the Longridge Prize

For the greatest proficiency evinced during the three years immediately preceding, on the Sessional Examinations for Honours in the classes of the Faculty of Medicine of the College; and for creditable performance of duties of offices at the Hospital

that included a £40 stipend.178 He was also awarded a gold medal in structural and physiological botany.179180 Lister won two of the four available gold medals in anatomy and physiology as well as surgery, which came with a scholarship of £50 a year for two years, for his second examination in medicine.181 In the same year, Lister passed the examination for the fellowship of the Royal College of Surgeons,182 bringing to a close nine years of education.183

Sharpey advised Lister to spend a month at the medical practice of his lifelong friend James Syme in Edinburgh and then visit medical schools in Europe for a longer period for training.184 Sharpey himself had been taught first in Edinburgh and later in Paris. Sharpey had met Syme, a teacher of clinical surgery widely considered the best surgeon in the United Kingdom185 while he was in Paris.186 Sharpey had gone to Edinburgh in 1818,187 along with many other surgeons since, due to the influence of John Hunter.188 Hunter had taught Edward Jenner, seen as the first surgeon to take a scientific approach to the study of medicine, known as the Hunterian method189 Hunter was an early advocate for careful investigation and experimentation,190 using the techniques of pathology and physiology to give himself a better understanding of healing than many of his colleagues.191 For example, his 1794 paper, A treatise on the blood, inflammation and gun-shot wounds192 was the first systematic study of swelling,193 discovering that inflammation was common to all diseases.194 Due to Hunter, surgery, then practised by hobbyists or amateurs, became a true scientific profession.195 As the Scottish universities taught medicine and surgery from a scientific viewpoint, surgeons who wished to emulate those techniques travelled there for training.196 Scottish universities had several other features that distinguished them from those in the south.197 They were inexpensive and did not require religious admissions tests, and thus attracted the most scientifically progressive students in Britain.198 The most important differentiator was that medical schools in Scotland had evolved from a scholarly tradition, where English medical schools relied on hospitals and practice.199 Experimental science had no practitioners at English medical schools and while Edinburgh University medical school was large and active at the time, southern medical schools were generally moribund, and their laboratory space and teaching materials inadequate.200 English medical schools also tended to view surgery as manual labour, not a respectable calling for a gentleman academic.201

Surgical profession 1854

Before Lister's studies of surgery, many people believed that chemical damage from exposure to "bad air", or miasma, was responsible for infections in wounds.202 Hospital wards were occasionally aired out at midday as a precaution against the spread of infection via miasma, but facilities for washing hands or a patient's wounds were not available. A surgeon was not required to wash his hands before seeing a patient; in the absence of any theory of bacterial infection, such practices were not considered necessary. Despite the work of Ignaz Semmelweis and Oliver Wendell Holmes Sr., hospitals practised surgery under unsanitary conditions. Surgeons of the time referred to the "good old surgical stink" and took pride in the stains on their unwashed operating gowns as a display of their experience.203

Edinburgh 1853–1860

James Syme

Syme, a well-established clinical lecturer at Edinburgh University for more than two decades before he met Lister,204 was considered the boldest and most original surgeon then living in Great Britain.205 He became a surgical pioneer during his career, preferring simpler surgical procedures, as he detested complexity,206 in the era that immediately preceded the introduction of anaesthesia.207

In September 1823, at the age of 24, Syme made a name for himself by first performing an amputation at the hip-joint,208209 the first in Scotland. Considered the bloodiest operation in surgery, Syme completed it in less than a minute,210211 as speed was essential at that time, before anaesthesia. Syme became widely known and acclaimed for developing a surgical operation that became known as Syme amputation, an amputation at the ankle where the foot is removed and the heel pad is preserved.212 Syme was considered a scientific surgeon, as evidenced by his paper On the Power of the Periosteum to form New Bone,213 and became one of the first advocates of antiseptics.

Arrival in Edinburgh

In September 1853, Lister arrived in Edinburgh bearing letters of introduction from Sharpey to Syme.214 Lister was anxious about his first appointment but decided to settle in Edinburgh after meeting Syme, who embraced him with open arms, invited him to dinner, and offered him an opportunity to assist him in his private operations.215

Lister was invited to Syme's house Millbank in Morningside (now part of Astley Ainslie Hospital),216 where he met, amongst others, Agnes Syme, Syme's daughter from another marriage and granddaughter of physician Robert Willis.217218 While Lister thought that Agnes was not conventionally pretty, he admired her quickness of mind, her familiarity with medical practice, and her warmth.219 He became a frequent visitor to Millbank and met a much wider group of eminent people than he would have in London.220

In the same month, Lister began assisting Syme at the University of Edinburgh221 In a letter to his father, Lister expressed surprise at the size of the infirmary and spoke about his impressions of Syme, "..is larger than I expected to find it; there are 200 Surgical beds, and a large number in other departments. At University College Hospital there were only about 60 Surgical beds, so altogether a prospect appears to be opening of a very profitable stay here. ...Syme is, I suppose, the first of British surgeons, and to observe the practice and hear the conversation of such a man is of the greatest possible advantage".222 By October 1853, Lister decided to spend the winter in Edinburgh. Syme was so impressed by Lister, that after a month Lister became Syme's supernumerary house surgeon at the Royal Infirmary of Edinburgh223 and his assistant in his private hospital at Minto House in Chambers Street.224 As house surgeon, Lister assisted Syme during every operation, taking notes.225 It was a much-coveted position226 and gave Lister the option of choosing which of the ordinary cases he would attend.227 During this period, Lister presented a paper at the Royal Edinburgh Medico-Chirurgical Society on the structure of cancellous exostoses that had been removed by Syme, demonstrating that the method of ossification of these growths is the same as that which occurs in epiphyseal cartilage.228

In September 1854, Lister's house surgeoncy appointment was finished.229 With the prospect of being out of a job, he spoke to his father about seeking a position at the Royal Free Hospital in London.230 However, Sharpey had written to Syme warning him that it was unlikely that Lister would be welcome at the Royal Free as he would have likely eclipsed Thomas H. Wakley, whose father held considerable sway at the hospital.231 Lister then made plans to tour Europe for a year.232 However, an opportunity presented itself with the death of noted infirmary surgeon and surgical lecturer at the Edinburgh Extramural School of Medicine Richard James Mackenzie.233 Mackenzie had been seen as a successor to Syme234 but had contracted cholera in Balbec in Scutari, Istanbul, while on a four-month volunteer sabbatical as field surgeon to the 79th Highlanders during the Crimean War.235 Lister proposed to Syme that he take over Mackenzie's position and become assistant surgeon to Syme.236 Syme initially rejected the idea, as Lister was not licensed to operate in Scotland, but later warmed to the idea.237 In October 1854, Lister was appointed as a lecturer238Lister successfully transferred the lease held by Mackenzie at his lecture room at 4 High School Yards, to himself. On 21 April 1855, Lister was elected a Fellow of the Royal College of Surgeons of Edinburgh239 and two days later rented a home at 3 Rutland Square.240 In June 1855, Lister made a hurried trip to Paris to take a course on operative surgery on the dead body and returned in June.241

At the Royal InfirmaryJoseph Lister c. 1855Lister with his colleagues at the Old Royal InfirmaryThe old infirmary

Extramural lecturing

On 7 November 1855, Lister gave his first extramural lecture on the "Principles and Practice of Surgery", in a lecture theatre at 4 High School Yards242 known as Old Jerusalem, directly located across from the infirmary.243 His first lecture was read from 21 pages of foolscap folio.244 Lister's first lectures were based on notes, either read or spoken, but over time he used notes less and less,245 becoming extempore in his speech, slowly and deliberately forming his argument as he went along.246 With this deliberate way of speaking, he managed to overcome a slight, occasional stammer which in his early days had been more pronounced.247

His first student was John Batty Tuke,248 in a class of nine or ten, mostly consisting of dressers.249 Within a week, twenty-three people had joined.250 In the next year, only eight people turned up. In the summer of 1858, Lister had the ignominious experience of reading his lecture to a single student, who arrived ten minutes late. Seven more students arrived later.251

His first lecture focused on the concept of surgery, giving a definition of disease that linked it to the Hippocratic Oath.252 He then explained that surgery could have more benefits than medicine, which could only comfort the patient at best. He then explained the attributes a good surgeon should exhibit, before finishing the lecture by recommending Syme's book "Principles of Surgery". Lister completed 114 lectures that followed a standard syllabus. Lecture VII described his earliest experiment on inflammation, where he put mustard on his arm and watched the results. Lectures IV to IX dealt with the circulation of blood. Inflammation was discussed in lectures X to XIII. The second half of the course dealt with clinical surgery. For the last four days, he gave two lectures a day, to complete the event before his wedding, with the first course ending on 18 April 1856.253 In the summer of 1858, Lister started a second, completely separate course, where he lectured on surgical pathology and operative surgery.254

Marriage

By mid-summer 1854, Lister had started to court Agnes Syme.255 Lister wrote to his parents about his love but they worried about the union, particularly since he was Quaker and Agnes had given no indication that she would change her denomination.256 At that time when a Quaker married a person of another denomination, it was considered as marrying out of the society.257 Lister was determined to marry Agnes and sent a further letter to his father, asking him if his financial support would continue should Lister and Agnes marry. Lister's father replied that Agnes not being in the Society of Friends would not affect his pecuniary arrangements258 and offered his son extra money to buy furniture and suggested that Syme would offer a dowry and that he would negotiate with Syme directly on it.259 His father suggested that Lister voluntarily resign from the Society of Friends.260 Lister made up his mind and subsequently left the Quakers to become a Protestant, later joining the congregation of the Saint Paul's Episcopal Church in Jeffrey Street, Edinburgh.261 In August 1855, Lister became engaged to Agnes Syme262 and on 23 April 1856 married her in the drawing room of Millbank, Syme's house in Morningside.263 Agnes's sister stated that this was out of consideration of any Quaker relations.264 Only the Syme family were present.265 The Scottish physician and family friend John Brown toasted the couple after the reception.266

The couple spent a month at Upton and the Lake District,267 followed by a three-month tour of the leading medical institutes in France, Germany, Switzerland, and Italy.268 They returned in October 1856.269 By this time, Agnes was enamoured with medical research and became Lister's partner in the laboratory for the rest of her life.270 When they returned to Edinburgh, the couple moved into a rented house at 11 Rutland Street in Edinburgh.271 The house was situated over three floors with a study on the first floor, that was converted into a consulting room for patients and a room with hot and cold taps on the second floor that became his laboratory.272 The Scottish surgeon Watson Cheyne, who was almost a surrogate son to Lister, stated after his death that Agnes had entered into her work wholeheartedly, had been his only secretary, and that they discussed his work on an almost equal footing.273

Lister's books are full of Agnes' careful handwriting.274 Agnes would take dictation from Lister for hours at a stretch. Spaces would be left blank amongst the reams of Agnes' handwriting for small diagrams, that Lister would create using the camera lucida technique and Agnes would later paste in.275

Lister's familyJames Syme, c. 1855Photogravure of Agnes "Aggie" Syme in 1856, taken by Sir Emery Walker in 1924Wedding photograph of the couple, taken in April 1856

Assistant surgeoncy

On 13 October 1856, he was unanimously elected to the position of Assistant Surgeoncy at Edinburgh Royal Infirmary.276 In 1856 he was also elected a member of the Harveian Society of Edinburgh.277278

Contributions to physiology and pathology 1853–1859

Between 1853 and 1859 in Edinburgh, Lister conducted a series of physiological and pathological experiments. His approach was rigorous and meticulous in both measurement and description.279 Lister was clearly aware of the latest advances in physiological research in France, Germany, and other European countries280 and maintained an ongoing discussion of his observations and results with other leading physicians in his peer group including Albert von Kölliker, Wilhelm von Wittich, Theodor Schwann, and Rudolf Virchow281 and ensured he correctly cited their work.

Lister's primary instrument of research was his microscope and his primary research subjects were frogs. Before his honeymoon, the couple had visited his uncle's house in Kinross.282 Lister took his microscope and captured several frogs, intending to use them in the study of inflammation, but they escaped.283 When he returned from his honeymoon, he used frogs captured from Duddingston Loch in his experiments.284 Lister carried out his experiments in his laboratory and in the veterinary college abattoir, on animals that were either dead or chloroformed and pithed, to deprive it of sensation.285 He also used bats, sheep, cats, rabbits, oxen and horses in his experiments.286 Lister's tirelessness in his pursuit of knowledge was illustrated by his assistant Thomas Annandale, who stated:

I confess that on more than one occasion our patience was a little tried by the long hours were thus engaged, and more particularly when the dinner hour was many hours overdue, but no one could work with Mr. Lister without imbibing some of his enthusiasm.287

These experiments resulted in the publication of eleven papers between 1857 and 1859.288 They included the study of the nervous control of arteries, the earliest stages of inflammation, the early stages of coagulation, the structure of nerve fibres, and the study of the nervous control of the gut with reference to sympathetic nerves.289 He continued these experiments for three years until he was appointed to a position at the University of Glasgow.290

1855: Beginning of inflammation research

In a letter dated 16 September 1855, Lister recorded the beginnings of his research into inflammation, six weeks before his lectures were to begin.291 Later in life, Lister stated that he considered his research into inflammation to have been an "essential preliminary" to his conception of the antiseptic principle and insisted that these early findings be included in any memorial volume of his work.292 In 1905, when he was seventy-eight years old, he wrote,

If my works are read when I am gone, these will be the ones most highly thought of.293

Inflammation is defined by four symptoms, heat, redness, swelling and pain.294 Surgeons prior to Lister saw it as the signal for the arrival of suppuration or putrefaction, local or general infection.295 As the germ theory of disease had not yet been discovered, the concept of infection did not yet exist.296 However, Lister knew that slowing of the blood through the capillaries seemed to precede inflammation.297 Joseph Jackson Lister had written a paper with Thomas Hodgkin that described how blood cells behaved prior to a clot, i.e. specifically how the concave cells fitted themselves together into stacks.298 Lister knew that to observe the next step, it was important that the tissue remain alive so the blood vessels could be observed through the microscope.299

In September 1855, Lister's first experiment was on the artery of a frog viewed under his microscope, subjected to a water droplet of differing temperatures, to determine the early stage of inflammation.300301 He initially applied a water droplet at 80 °F (27 °C) which caused the artery to contract for a second and the flow to cease, then dilate as the area turned red and the flow of blood increased.302 He progressively increased the temperature to 200 °F (93 °C). The blood slowed down and then coagulated.303 He continued the experiment on the wing of a chloroformed bat to widen his research focus.304 Lister concluded that the contraction of the vessels led to the exclusion of blood cells from the capillaries, not their arrest, and that blood serum continued to flow. This was his first independent discovery.305

Frog's web prepared by Joseph Lister, 1857Specimen of common frog that Lister used in his early experimentsSpecimen of common bat found at Duddingston Loch that Lister experimented on

The experiments ceased between October 1855 and continued in September 1856 when the couple moved into Rutland Square.306 Lister started with mustard as an irritant, then Croton oil, acetic acid, oil of Cantharidin and chloroform and many others.307 These experiments led to the production of three papers. His first paper grew out of the need to prepare for these extramural lectures and had begun the year before, continuing in development for six weeks after he moved into Rutland Street.308 The early paper, titled: "On the early stages of inflammation as observed in the Foot of a Frog" was read to the Royal College of Surgeons of Edinburgh on 5 December 1856. The last third was read out extempore.309

1856 Beginning of coagulation research

Lister also conducted research into the process of coagulation during this period.310 He had observed inflammation in certain cases of septicaemia that affected the blood vessel's lining, and led to intravascular blood clotting,311 which led to putrefaction and secondary haemorrhage.312 A simple experiment in December 1856 described by Agnes, where he pricked his own finger to observe the process of coagulation.313 led to five physiology papers on coagulation between 1858314 and 1863.315

Several competing theories explained the occurrence of a blood clot, and although the theories were largely abandoned, it was still thought that blood contained a liquifying agent,316 i.e. fibrin held in a solution of ammonia317 that became known as the "Ammonia theory".318

In 1824, Charles Scudamore had proposed carbonic acid as the solution.319 The prevailing theory was from Benjamin Ward Richardson, who won the 1857 Astley Cooper triennial prize for an essay where he postulated that blood remained liquid due to the presence of ammonia. In the same year, Ernst Wilhelm von Brücke proposed that the vital actions of the vessels inhibited the blood's natural tendency to coagulate.320

1856 On the minute structure of involuntary muscle fibre

Lister's third paper,321322 published in 1858 in the same journal and read before the Royal Society of Edinburgh on 1 December 1856,323 concerned the histology and function of the minute structures of involuntary muscle fibres.324 The experiment, conducted in the autumn of 1856,325 was designed to confirm Kölliker's observations on the structure of individual muscle fibres.326 Kölliker's description had been criticised, as he had used needles to separate the tissue to observe individual cells, and his critics said that he had observed artefacts from the experiment rather than real muscle cells.327 Lister proved conclusively that the muscle fibres of blood vessels, described by Lister as slightly flattened and elongated,328 were similar to those found by Kölliker in pig intestine, but wrapped spirally and individually around the innermost membrane.329 He stated that the variations in shape, from long tubular bodies with pointed ends and elongated nuclei to short "spindles" with squat nuclei, represented different phases of muscular contraction.330 During the "Huxley Lecture" he stated in retrospect, that he could not imagine a more efficient mechanism to constrict these vessels.331

1857 On the flow of the lacteal fluid in the mesentery of the mouse

His next paper332 was a short report based on observations that he had made in 1853.333 This first experiment, as opposed to purely microscope work,334 determined the nature of the flow of chyle in the lymphatics and whether the lacteals in the gastrointestinal wall could absorb solid granules from the lumen.335 For the first experiment, a mouse fed beforehand on bread and milk was chloroformed and then had its abdomen opened and a length of intestine placed on glass under a microscope.336 Lister repeated the experiment several times and each time saw mesenteric lymph flowing in a steady stream, without visible contractions of the lacteals. For the second experiment, Lister dyed some bread with indigo dye and fed it to a mouse, with the result that no indigo particles were ever seen in the chyle.337 Lister delivered the paper to the 27th meeting of the British Medical Association, held in Dublin 26 August to 2 September 1857.338 The paper was formally published in 1858 in the Quarterly Journal of Microscopical Science.339

Seven papers on the origin and mechanism of inflammation

In 1858, Lister published seven papers on physiological experiments he conducted on the origin and mechanism of inflammation.340 Two of these papers were research into the neural control by the nervous system of blood vessels, "An Inquiry Regarding the Parts of the Nervous System Which Regulate the Contractions of the Arteries" and "On the Cutaneous Pigmentary System of the Frog", while the third and the principal paper in the series was titled: "On the Early Stages of Inflammation", which extended the research of Wharton Jones.341 The three papers were read to the Royal Society of London on 18 June 1857.342 They had originally been written as one paper and had been sent to Sharpey, John Goodsir and the English pathologist James Paget for review.343 However, Paget and Goodsir both recommended that it be published as three separate papers.344345

1858 An Inquiry Regarding the Parts of the Nervous System Which Regulate the Contractions of the Arteries

During 1856, Lister has been thinking about the nervous control of blood vessels and had been studying the work of various French researchers who were examining the denervation of the sympathetic nerves.346 Lister thought that how blood vessels behaved when irritated was important to understand the inflammatory process.347

The experiments on vasomotor control began in the autumn of 1856 and continued until the autumn of the next year.348 In total, Lister conducted 13 experiments, some of which were repeated to verify the results of other experiments in the series.349 He used a microscope fitted with an ocular micrometer, a recent invention, to measure the diameter of blood vessels in a common frogs web. In a before and after experiment, he ablated parts of the central nervous system350 and also before and after, split the sciatic nerve.351 Lister concluded that blood vessel tone352 was controlled from the medulla oblongata and the spinal cord.353 This refuted Wharton's conclusions, in his paper Observations on the State of the Blood and the Blood-Vessels in Inflammation.354 who was not able to confirm that the control of blood vessels of the hind legs was dependent upon spinal centres.355

In October 1857, the referee for Philosophical Transactions John Goodsir wrote to Sharpey who warned Lister that the experimental conclusions were similar to findings by the German physiologist Eduard Friedrich Wilhelm Pflüger.356 This was to enable Lister to print an acknowledgement.357 Pflüger found that vasomotor control was through nerve fibres connected to the spinal canal which were similar to Lister research showing vaso-motor fibres came from the spinal canal through the sciatic plexus.358 Although their approaches were similar, Lister used denervation and discovered that even after parts of the spinal cord were removed, the arterioles eventually recovered their contractility.359

These experiments360 settled a contemporary dispute between physiologists concerning the origin of the influence exercised over blood vessel diameter (calibre) by the sympathetic nervous system.361 The dispute began when Albrecht von Haller formulated a new theory known as Sensibility and Irritability in his 1752 thesis De partibus corporis humani sensibilibus et irritabilibus. The dispute had been debated since the middle of the 18th century. Haller put forward the view that contractability was a power inherent in the tissues which possessed it, and was a fundamental fact of physiology.362 It concerned the property of irratability, the supposed automatic response of muscular tissue, especially visceral tissue, to external stimulus, that caused them to contract when stimulated.363 Even as late as 1853, highly respected textbooks, for example William Benjamin Carpenter Principles of Human Physiology stated the doctrine of 'irritability' was a fact beyond dispute,364 and this was still considered contentious when John Hughes Bennett created the Physiology article for the 8th edition of Encyclopædia Britannica in 1859.365

1858 On the Cutaneous Pigmentary System of the Frog

The second part of the original paper366 was an experiment into the nature and behaviour of pigment.367 It had been known for some years that the skin of frogs is capable of varying in colour under different circumstances.368 The first account of this mechanism had been first described by Ernst Wilhelm von Brücke of Vienna in 1832369 and later investigated further by Wilhelm von Wittich in 1854370 and Emile Harless in 1947.371

Lister had noted that the beginning of inflammation was always accompanied by a change of colour in the frog's web.372 He determined that the pigments consisted of "very minute pigment-granules" contained in a network of stellate cells, the branches of which, subdividing minutely and anastomosing freely with one another and with those of neighbouring cells, constitute a delicate network in the substance of the true skin.373 It had been supposed that the concentration and diffusion of the pigment depended upon the contraction and extension of the branches of the star-shaped cells in which it was contained; and that only these movements of the cells were under the influence of the nervous system. At the time, there was no cell theory of matter nor were there any dyes or fixatives that could used to enhance experimental discovery.374 Indeed, Lister wrote of this, stating "The extreme delicacy of the cell wall makes it very difficult to trace it among the surrounding tissue".375 Lister observed that it was the pigment granules themselves and not the cells that moved, and that this movement was not merely brought about by the control of the nervous system, but perhaps by the direct action of irritants on the tissues themselves.376 He believed that the pigment reflected the activity of blood vessels, though it was the slowing of blood flow that initiated the process of inflammation.377

1858 On the early stages of inflammation

The focal study378 was the longest paper of the three and the last to be published.379 Like many of his colleagues, Lister was aware that inflammation was the first stage of many postoperative conditions380 and that excessive inflammation often preceded the onset of a septic condition.381 Once that happened, the patient would develop a fever.382 Lister had come to the conclusion that accurate knowledge of the functioning of inflammation could not be obtained by researching the more advanced stages, which were subject to secondary processes.383 He therefore started in quite a different way from that of almost all his predecessors by directing his enquiry to the very first deviations from health, hoping to find in them "the essential character of the morbid state most unequivocally stamped".384 Essentially, Lister performed these experiments to discover the causes of erythrocyte adhesiveness. As well as experimenting on frogs' web and bats wing,385 Lister used blood that he had obtained from the end of his own finger that was inflamed and compared it against blood from one of his other fingers.386 He discovered that after something irritating had been applied to living tissues which did not kill them outright, firstly the blood vessels contracted and their lumen became very small; the part became pale. Secondly, the vessels after an interval, dilated and the part became red. Thirdly, some of the blood in the most injured blood vessels slowed down in its flow and coagulated. Redness occurred which, being solid, could not be pressed away. Lastly, the fluid of the blood passed through the vessel walls and formed a "blister" about the seat of injury.387 He found that each tiny artery was surrounded by a muscle, which enables it to contract and dilate. He found further that this contraction and dilation was not an individual act on its part, but was an act dictated to it by the nervous cells in the spinal cord.388

The paper was divided into four sections:

  • The aggregation of red blood cells when removed from the body, i.e., which occurs during coagulation.
This section deals with the aggregation of the cells of the blood, which occurs during the process of clotting. It shows that when blood is removed from the body this aggregation depends on their possessing a certain degree of mutual adhesiveness, which is much greater in the white blood cells than in the red blood cells. This property, though apparently not depending upon vitality, is capable of remarkable variations, in consequence of very slight chemical changes in the blood plasma.389
  • The structure and function of blood vessels.
This section shows that the arteries regulate, by their contractility, the amount of blood transmitted in a given time through the capillaries, but that neither full dilatation, extreme contraction, nor any intermediate state of the arteries, is capable per se of producing accumulation of blood cells in the capillaries.390
  • The effects of irritants on blood vessels, e.g., hot water.
This section details how the effects are two-fold
  • firstly, a dilatation of the arteries (commonly preceded by a brief period of contraction), which is developed through the nervous system and is not confined to the part brought into actual contact with the irritant, but implicates a surrounding area of greater or less extent; and
  • secondly, an alteration in the tissues upon which the irritant directly acts, which makes them influence the blood in the same manner as does ordinary solid matter. This imparts adhesiveness to both the red and the white blood cells, making them prone to stick to one another and to the walls of the vessels, and so gives rise, if the damage to the tissues be severe, to stagnation of the blood flow and ultimately to obstruction.391
  • The effects of irritants on tissue.392
The fourth section describes the effects of irritants upon the tissues. It proves that those which destroy the tissues when they act powerfully, produce by their gentler action only a condition bordering on loss of vitality, i.e. a condition in which the tissues are incapacitated, but from which they may recover, provided the irritation has not been too severe or protracted.393

Lister's paper was able to show that capillary action is governed by the constriction and dilation of the arteries. The action is affected by trauma,394 irritation or reflex action through the central nervous system.395 He noticed that although the capillary walls lack muscle fibres, they are very elastic and are subject to significant capacity variations that are influenced by arterial blood flow into the circulatory system.396 Drawings made with a camera lucida were used to depict the experimental reactions.397 They displayed vascular stasis and congestion in the early stages of the body's reaction to damage. According to Lister, vascular alterations that were initially brought on by reflexes occurring within the nervous system were followed by changes that were brought on by local tissue damage. In the conclusions of the paper, Lister linked his experimental observations to physical clinical conditions, for example skin damage resulting from boiling water and trauma occurring after a surgical incision.398

After the paper was read to the Royal Society in June 1857, it was very well received and his name became known outside Edinburgh.399

Camera lucida illustrations from this paperFrogs web that has been irritated with mustard

On a Case of Spontaneous Gangrene from Arteritis, and on the Causes of Coagulation of the Blood in Diseases of the Blood-Vessels

Lister's first paper is an account of a case of spontaneous gangrene in a child.400 The paper on coagulation401 was read before the Medico-Chirugical Society of Edinburgh on 18 March 1858.402 In an account written by Agnes, she states that there was no one at the medical school meeting who was capable of appreciating it, and the remarks made upon it were very poor. There were suggestions for improvement which Lister threw out. There was lots of cheering, proclaiming it a great success. The paper was written up at 7pm, with Lister dictating and Agnes writing it during a 50-minute session, followed by the exposition to the society at George Street hall at 8pm.403

Lister first used the amputated legs from sheep and discovered that blood remained liquid in the blood vessels for up to six days and still underwent coagulation, albeit more slowly when the vessel was opened. He also noticed that if vessels remained fresh, the blood would remain fluid.404 In later experiments he moved to cats.405 He tried to emulate an inflamed blood vessel by exposing the jugular vein of the animal and applying irritants then constricting and opening the flow, to measure the effect. He noticed that in the damaged vessel the blood would coagulate406407 He eventually came to the conclusion that if there was ammonia in the blood, it was much less important than the condition of the vessel in stopping coagulation.408 He tested his hypothesis on three cadavers by examining the condition of various veins and arteries and found he was correct.409 He also concluded that the Ammonia theory did not apply to vessels in the body, but it could apply to blood outside the body. While that was incorrect, his other conclusions were accurate.410 Specifically that inflammation in the blood vessel lining, results in coagulation occurring.411 Lister realised that vascular occlusion increased the pressure through the network of small vessels, leading to the formation of "liquor sanguinis"412 that lead to further localised damaged perfusion.413 Certainly, Lister had no knowledge of the coagulation cascade but his experiments contributed to the current understanding of clotting,414 the final product of coagulation.

Lister continued experimenting in April, examining vessels and blood from a horse. This resulted in another communication to the society on 7 April.415 His work in coagulation continued until the end of the year. Lister's second article on coagulation was published in August 1858, and was one of two case histories he published in the Edinburgh Medical Journal in 1858.416 Titled: "Case of Ligature of the Brachial Artery, Illustrating the Persistent Vitality of the Tissues".417 The history described saving a patient's arm from being amputated which had been constricted by a tourniquet for thirty hours.418 The second history was titled "Example of mixed Aortic Aneurysm" and published in December 1858.419

1858 Preliminary account of an inquiry into the functions of the visceral nerves

Lister continual interest in the nervous control of blood vessels led him to conduct a series of experiments during June and July 1858, where he researched the nervous control of the gut.420 The research was published in the form of three letters sent to Sharpey. The first two letters were sent on 28 June and 7 July 1858421 The last letter was published as the "Preliminary Account of an Inquiry into the Functions of the Visceral Nerves, with special reference to the so-called Inhibitory System.".422

He had been studying the work of Claude Bernard, LJ Budge and Augustus Waller and had become interested in what was known as "sympathetic action", where inflammation appeared in a different area from the source of irritation.423 This led him to study Pflüger's 1857 paper titled "About the inhibitory nervous system for the peristaltic movements of the intestines",424 proposed that the splanchnic nerves instead of exciting the intestine muscle layer that they are connected to, inhibit their movement.425 The German physiologist Eduard Weber made the same claim.426 Pflüger had named these inhibitory nerves "Hemmungs-Nervensystem", a name that Syme, at Lister's request thought they should be translated as inhibitory nervous system.427 Lister dismissed Pflüger's idea of inhibitory nerves as not only implausible but not supported by observation,428 as a mild stimulus caused increased muscle activity which changed to a decreased muscle activity as the incoming stimulus became stronger.429 Lister believed that it was questionable whether the motions of the heart or the intestines are ever checked by the spinal system, except for very brief periods.430

Lister conducted a series of experiments using mechanical irritation and galvanism to stimulate the nerves and spinal cord in rabbits and frogs.431 and due to rabbits active gut movement, he considered them ideal for the experiment.432 To ensure their gut reflexes were not impaired, the rabbits were not anaesthetised.433 Lister conducted three experiments. In the first experiment, an incision was made in the rabbit's side and a section of intestine was pulled through the skin. Lister then connected a magnetic coil battery to the splanchnic nerves in the spinal cord. When the current was applied, the gut completely relaxed but when the current was applied locally, a small localised contraction occurred that did not spread to the bowel.434 Lister stated that "this observation is of fundamental importance, since it proves that the inhibitory influence does not operate directly upon the muscular tissue, but upon the nervous apparatus by which its contractions are, under ordinary circumstances, elicited".435 In the second experiment, Lister examined the reaction in a section of the bowel, when he restricted the blood supply by tying the vessels and found that there was an increase in peristalsis. When he applied current the gut relaxed. He concluded that activity in the gut was under the control of bowel wall nerves and had been stimulated due to loss of blood.436 In the third experiment, he removed the nerves from a section of the bowel while ensuring to maintain a good blood supply. This time, stimulation of the section had no effect except when the section would spontaneously contract.

During the histological study of the bowel wall, Lister discovered a plexus of neurons437 the myenteric plexus, that confirmed the observations made by Georg Meissner in 1857.438439

Lister concluded, "...it appears that the intestines possess an intrinsic ganglionic apparatus which is in all cases essential to the peristaltic movements, and, while capable of independent action, is liable to be stimulated or checked by other parts of the nervous system".440

Although Lister did not believe in the inhibitory system, he did conclude that extrinsic nerves controlled the intestinal motor function indirectly through their effect on the plexus. It was not until 1964 that this was proven by Karl‐Axel Norberg.441

Notice of further researches on the coagulation of the blood

Lister's third paper on coagulation442 was a short article in the form of a communication consisting of five pages that were read before the Medico-Chirugical Society of Edinburgh on 16 November 1859. In the paper, Lister found that the coagulation of blood was not solely dependent on the presence of ammonia, but may also be influenced by other factors. In a demonstration before the society, Lister had a sample of horse's blood that had been shed twenty-nine hours earlier and added acetic acid to it. The blood remained fluid despite being acidified, but it eventually coagulated after being left to stand for 15 minutes. Lister demonstrated that the Ammonia theory was incorrect as the coagulation of the blood was not dependent on the presence of ammonia. He concluded that other factors may influence blood coagulation in addition to or instead of ammonia, and that the Ammonia theory was fallacious.443

Glasgow appointment

On 1 August 1859, Lister wrote to his father to inform him of the ill-health of James Adair Lawrie, Regius Professor of Surgery at the University of Glasgow, believing he was close to death.444 The anatomist Allen Thomson had written to Syme to inform him of Lawrie's condition and that it was his opinion that Lister was the most suitable person for the position.445 Lister stated that Syme believed he should become a candidate for the position.446 He went on to discuss the merits of the post; a higher salary, being able to undertake more surgery and being able to create a bigger private practice.447 Lawrie died on 23 November 1859.448 In the following month, Lister received a private communication, although baseless, that confirmed he had received the appointment.449 However, it was clear the matter was not settled when a letter appeared in the Glasgow Herald on 18 January 1860 that discussed a rumour that the decision had been handed over to the Lord Advocate and officials in Edinburgh.450451 The letter annoyed the members of the governing body of Glasgow University, the Senatus Academicus. The matter was referred to the Vice-Chancellor Thomas Barclay who tipped the decision in favour of Lister.452 On 28 January 1860, Lister's appointment was confirmed.453

Glasgow 1860–1869

University life

To be formally inducted into the academic staff, Lister had to deliver a Latin oration before the senatus academicus.454 In a letter to his father, he described how surprised he was when a letter arrived from Allen Thomson informing him that the thesis had to be presented the next day on 9 March. Lister unable to start the paper until 2 am that night, had only prepared around two-thirds of it, when he arrived in Glasgow. The rest was written at Thomson's house. In the letter, he described the dread he felt being admitted into the room prior to presenting the oration. After the thesis was read and Lister was inducted to the senate, he signed a statement not to act contrary to the wishes of the Church of Scotland.455 While the contents of his thesis have been lost, the title is known, "De Arte Chirurgica Recte Erudienda" ("On the proper way of teaching the art of surgery").456

In early May 1860, the couple made the journey to Glasgow to move into their new house at 17 Woodside Place, at the time on the western edge of the city.457 In 1860, university life in Glasgow was lived in the grimy quadrangles of the small college on Glasgow High Street, a mile east of the city centre next to Glasgow Royal Infirmary (GRI) and the Cathedral and surrounded by the most squalid part of the old medieval city.458 The Scottish poet and novelist Andrew Lang wrote of his student days at the college, that while Coleridge could smell 75 different stenches during his student days in Cologne, Lang counted more.459 The city was so polluted the grass did not grow.

The position of Professor of Surgery at Glasgow was peculiar, as it did not carry with it an appointment as surgeon to the Royal Infirmary, as the university was separate from the hospital. The allotment of surgical wards to the care of the Professor of Surgery depended upon the goodwill of the directors of the infirmary.460 His predecessor Lawrie never held any hospital appointments at all.461 Having no patients to care for, Lister immediately began a summer lecture course. He discovered that college classrooms were considered too small and had low ceilings for the number of students, which made them unpleasant to be in when filled to overcrowding.462 Before his first lecture, the couple cleaned and painted the dingy lecture room assigned to them, at their own expense.463 He inherited a large class of students from his predecessor that grew rapidly.464

After his first session, he wrote favourably of Glasgow:

The facilities I have here for prosecuting this course as compared to the difficulties I laboured under in Edinburgh are quite delightful – museums, abundant material and a good library all at my disposal and my colleague Allen Thompson co-operating in the kindest and most valuable manner465

Glasgow university lifeWoodside PlaceThe old collegeThe old college entranceGlasgow high street from the collegeGlasgow Royal InfirmaryThe surgical houseEntrance to male ward 24

In August 1860, Lister was visited by his parents, who took a "saloon" carriage on the Great Northern Railway.466 In September 1860, Marcus Beck came to live with the Listers and their two servants, while he studied medicine at the university.467 In the closing weeks of the summer, the Listers along with Beck, Lucy Syme and Ramsay went on a short holiday to Balloch, Loch Lomond. While the group was visiting Tarbet, Argyll, the men rowed across the loch and ascended Ben Lomond.468

Election to surgeoncy

In August 1860, Lister had been rejected for a post at the Royal Infirmary by David Smith, a shoemaker who was the chairman of the hospital board.469 When Lister put his case to Smith explaining the need for anatomical demonstrations so the students could understand the practice of surgery, Smith stated his belief that "the infirmary was a curative institution, not an educational one".470 The rejection both annoyed and surprised Lister as he had been promised by Thomson that the position was assured.471 Indeed, he had informed his father of the fact that the post was guaranteed in his letter to his father.472

In November 1860, the winter lecture course began. In total 182 students registered for the lectures473 and according to Godlee it was likely the "largest class of systematic surgery in Great Britain, if not in Europe".474 The class consisting of mostly 4th year students with some 3rd and 2nd year students, was so enthused, that they decided to make Lister the Honorary President of their Medical Society.475 When the time approached for the election to the surgeoncy in 1861, 161 students signed a petition on parchment supporting his claim for election.476 Lister was not elected until 5 August 1861, in what was described by Beck as a "troublesome canvas".477 Lister was put in charge of wards XXIV (24) and XXV (25) in October 1861.478 It was not until November 1861 that he performed his first public operation.479 Soon after Lister arrived at the GRI, a new surgical block was built and it was here that he conducted many of his trials of antisepsis.480

Holmes System of Surgery

Between the end of his winter lecture course and his appointment, Lister's correspondence contained little of scientific interest. A letter to his father dated 2 August 1861 explained why.481 He had halted his experiments on coagulation to work on two chapters, "Amputation" and "On Æsthetics" (On anaesthetics) for the medical reference work System of Surgery by Timothy Holmes, published in four volumes in 1862.482 Chloroform was Lister's preferred anaesthetic.483 He wrote three papers for Holmes in 1861, 1870 and 1882.484485 The science of anaesthesia was in its infancy486 when Lister first recommended chloroform to Syme in 1855, and he continued to use it until the 1880s.487 His sister Isabella Sophie first described it to him in 1848 when she had a tooth pulled. He had also used it without complications on three patients with tumours of the jaw in 1854.488 He classed it along with alcohol and opium as a "specific irritant" in "On the early stages of imflammation".489 Lister preferred it to ether, as it was safer to use in artificial light, protected the heart and blood vessels, and, Lister believed, gave the patient "mental tranquility" as it was the safest.490 In the 1871 edition, he reported that there had been no deaths in the Edinburgh or Glasgow infirmaries from chloroform, between 1861 and 1870.491 Lister described how his assistant applied the chloroform onto a simple handkerchief used as a mask and watched the patient's breathing. In 1870 however Lister updated the chapter to state that he felt apprehension about using chloroform on the "aged and infirm".492 In the same edition he recommended nitrous oxide for tooth extraction and the use of ether to avoid vomiting after abdominal surgery. In the winter of 1873, the English medical journals reported that sulphuric ether should be used instead but Watson Cheyne stated there had been no deaths from chloroform during the winter of 1873. In 1880, the British Medical Association recommended the synthetic gas ethidene dichloride for clinical trials. On 14 November 1881, Paul Bert published the dose-response curve of chloroform but Lister believed that smaller doses were sufficient to anaesthetize the patient.493 Starting in April 1882, Lister first conducted clinical research using ether and from July to November, lab experiments on chaffinches and then on himself and Agnes, to determine the correct dose.494 The 1882 chapter continued to recommend chloroform.495

The chapter on amputation was much more technical than the anaesthesia chapter, for example describing the ways of cutting the skin to produce flaps to close over the wound.496497 In the first edition, Lister examined the history of amputation from Hippocrates to Thomas Pridgin Teale, William Hey, François Chopart, Nikolay Pirogov and Dominique Jean Larrey498 and the discovery of the tourniquet by Etienne Morel.499 In the first edition, Lister devoted seven pages to dressings, but by the third edition used only a single sentence to recommend a dry dressing500 as opposed to the more common water dressing, thought to excluded air.501 By the third edition, Lister focused on describing three innovative surgical techniques. The first was a method for amputation through the thigh that he developed between 1858 and 1860, a modification of Henry Douglas Carden's technique for knee amputation.502 The thigh amputation went through the femoral condyles in a circular fashion with a small posterior flap that enabled a neat scar.503

The second technique was an aortic tourniquet for controlling blood flow in the abdominal aorta.504 The vessels of the aorta were too tough to close properly and ligatures either damaged the artery walls or caused premature death if left in too long.505 The third technique was a method of bloodless operation that he created in 1863–1864 by elevating a limb and quickly applying an india rubber tourniquet to stop limb circulation.506 It became unnecessary with the use of the Esmarch bandage.507 In 1859, he advocated for the use of silver wire sutures that had been invented by J. Marion Sims, but their use fell out of favour with the introduction of antiseptics.508

Croonian Lecture

On 1 January 1863, Lister returned to the topic of coagulation with the Croonian Lecture titled "On the coagulation of the blood",509 although it contained little that was new.510 The lecture, given in London at the invitation of the Royal Society and the Royal College of Physicians,511 began by reconfirming the fallacious nature of the ammonia theory, instead proposing that shed blood coagulates when the solid and fluid elements of the blood meet. His experiments had confirmed that blood plasma (liquor sanguinis) alone does not coagulate, but does when in contact with red blood cells.512 Lister suggested that living tissues possessed similar properties in relation to blood coagulation. He mentioned the presence of coagulable fluid in the interstices of cellular tissue and described instances of oedema liquid coagulating after emission, possibly due to a slight admixture of red blood cells.513 Lister highlighted the tendency of inflamed tissues to induce coagulation in their vicinity, suggesting that inflamed tissues temporarily lose their vital properties and behave like ordinary solids, leading to coagulation. He provided examples of inflamed arteries and veins exhibiting coagulation on their interior, like artificially deprived vessels.514 Lister then noted that inflamed tissues induce coagulation and oedema effusions remain liquid. He hypothesised that the accumulated red blood cells increased pressure in inflamed capillaries and contributed to the loss of healthy condition in capillary walls, leading to coagulation.515 In closing, Lister said his previous microscopic investigation published in the Philosophical Transactions, supported the view that tissues could be temporarily deprived of vital power by irritants. He proposed that inflammatory congestion arose from the adhesiveness of red blood cells to irritated tissues, like their behaviour outside the body when encountering ordinary solids. In finishing the lecture, Lister said he was satisfied that his previous conclusions on the nature of inflammation were independently confirmed through his research into blood coagulation.516

On excision of the wrist for caries

Lister's most original work that he undertook during 1863 and the beginning of 1864 was the development of a surgical technique for the excision of caries from the wrist, i.e., the removal of diseased bone due to tuberculosis.517 The procedure consisted of removing the ends of the bones entering into an articulation instead of amputating the whole limb, and was considered a recent development in "conservative surgery".518 Several surgeons had attempted the procedure. It was first performed by German surgeons Johann von Dietz in 1839 and Johann Ferdinand Heyfelder [de] in 1849, followed by British surgeon William Fergusson in 1851.519 While the development of techniques for excision of the elbow was largely successful, similar success for the excision of the wrist was elusive, so amputation was still considered the most appropriate treatment even in 1860.520 Lister developed a complicated technique that removed the tissue where the disease was likely to occur but preserved the structures used to move the fingers and wrist.521 The technique was adopted by the profession and the only complaint from surgeons was the length of the operation at 90 minutes.522 Lister waited almost a year before publishing the paper in March 1865 in The Lancet.523 The paper presented 15 case histories.524 In summary, ten people were cured, two had hopes of achieving a cure, two died of causes independent of the operation and Lister considered one operation unsatisfactory, a failure rate of 13%.525

Edinburgh position

Professor of Systematic Surgery in Edinburgh James Miller died in June 1864.526 The Edinburgh chair, considered the most prestigious within the Scottish medical community, came with an annual stipend of £700-£800 per year. Syme and his friends suggested that Lister should apply as his candidature was all but assured.527 A number of reasons have been advanced for why Lister applied. In a letter to his father, he said that he saw Glasgow as a stepping stone. There were a multitude of reasons to either stay or go. He was drawn to research, his friends were there, and he found the routine tasks in Glasgow to be "working in a corner". There was also the fact that his tenure only lasted 10 years.528 Testimonials from Christison, Paget, Buchanan and Syme followed the application. By the end of June, Lister was convinced the position was his.529 However, the chair went with James Spence instead.530 Lister was disappointed and in social settings tended to solipsism in conversation, but by October his father, in a letter said that it was, "very gratifying to learn thy complete reconcilement to remaining at Glasgow".531

Before he received the disappointing news, Lister had been called back to Upton as his mother Isabella was on her deathbed. She died on 3 September 1864.532 His father now lived alone at Upton as the only daughter left at home had married in 1858.533 Communication with his children became of paramount importance to Joseph Jackson and he started to send Lister a letter every week, stating in October "The thought that thou wilt look for letters from thee weekly, and the letters when they come, are alike gratifying to thy poor father."534

Winter lecture course

On 1 November, Lister began the winter lecture course, divided in two: common tissue and organ conditions, and conditions of physiology.535 His first lectures were on blood, then nerves, then detailed special nerves which explained the process of inflammation.536 In introducing the subject, he stated that any injury that did not cause death would result in inflammation with the familiar symptoms of redness, swelling and pain. These symptoms indicated "inflammatory congestion",537 the suspension of vital energy, beginning with red corpuscles adhering together, which was caused by fibrin, which itself was caused by two substances in the blood, one in the blood cells and one in liquor sanguis (plasma). He described two types of inflammation, direct and indirect. He saw direct inflammation as caused by a noxious agent and indirect by "sympathy", an indication that his frame of reference was wholly inadequate.538 He then provided various examples and examined various types of inflammation such as acute, latent and chronic. The following lectures explained how to alleviate the symptoms of inflammation, by for example elevating a limb to enable blood flow, or reducing tension by draining an abscess.539 The remarkable aspect of Lister's theory of inflammation was that while the details of his observations were correct, his theoretical structure to explain his observations was completely wrong. Lister's error lay in his belief that inflammation was a "unitary disease", a single underlying disease, when in effect it was a range of conditions.540 The second division of the lectures focused on the heart, blood vessels, lymphatic system, bones, joints and nerves.541

Christmas

Lister and Agnes spent Christmas 1864 with Joseph Jackson at Upton.542 In January, Lister attended a quite unusual operation by Syme in Edinburgh in which a patient's tongue was removed.543 A month later, Lister received an interesting letter from Jackson on fees that indicated Lister's growing private practice that he began in 1861. His practice was unusual, as it was solely dedicated to surgery, during a period when operations either took place at the doctor's surgery or at the patient's home.544 In March 1865, Lister and his colleagues became involved in the case of the murderer Edward William Pritchard who was employed as a doctor in Glasgow.545 Prichard had broken his oath. In a letter to his father, Lister expressed his sincere hope that he would be hung.546

Pasteur

At the end of 1864547 or during the spring of 1865548 (sources vary) while walking home with Thomas Anderson,549 the chemistry professor at Glasgow and discussing putrefaction, Anderson drew Lister's attention to the latest research of the French chemist Louis Pasteur,550 who had discovered living things that caused fermentation and putrefaction.551 Lister had not been a wide reader of continental literature,552 but began reading the weekly journal Comptes rendus hebdomadaires of the French Academy of Sciences in the years 1860-1863 where Pasteur discussed fermentation and putrefaction.553

The two papers that Anderson recommended to Lister were Sur les corpuscules organisés qui existent dans l'atmosphère, examen de la doctrine des générations spontanées 1861 (On the organized particles that exist in the atmosphere, examination of the doctrine of spontaneous generations).554 In this paper, Pasteur disproved the theory of spontaneous generation by proving the hypothesis that life in boiled infusions arose from spores.555 He also proved that particles in the air could be cultivated; and that if they were introduced from the air into a sterile liquid, they would reappear and multiply in the liquid.556 The second paper was Pasteur's magnum opus, titled Examen du rôle attribué au gaz oxygène atmosphérique dans la destruction des matières animales et végétales après la mort 1863 (Examination of the role attributed to atmospheric oxygen gas in the destruction of animal and plant matter after death),557 published 29 June 1863.558 The paper concluded that fermentation, putrefaction and slow combustion destroyed organic matter and these were necessary processes for life to exist.559 Pasteur learned that slow combustion was related to the anaerobic conditions when microorganisms were present.560

Several other papers would directly influence Lister's work on microorganisms.561 The third paper was the Mémoire sur la fermentation appelée lactique (Extrait par l'auteur) (Memoir on the so-called lactic acid fermentation (Extracted by the author)), published in 1857,562 described the discovery of the microbe responsible for fermentation in beer yeast.563 The fourth paper was the Memoire sur la Fermentation Alcoolique (Memoir on Alcoholic Fermentation), published in Annales de chimie et de physique in 1860.564 Pasteur described living microorganisms in yeast, Saccharomyces cerevisiae, that were responsible for the effervescent change that led to fermentation.565 The last paper by Pasteur was the Animalcules infusoires vivant sans gaz oxygène libre et déterminant des fermentations, (Animal Infusoria Living in the Absence of Free Oxygen and their fermentations)566 That paper, presented in 1861, was seminal in enabling Lister to understand the nature of sepsis,567 where the body's response to infections leads to injury of the tissue and organs. Pasteur's research led him to believe the ferment that produced Butyric acid was a microbe that lived in the absence of oxygen.568 The last paper that Lister found important was "Recherches sur la putréfaction" (Research on putrefaction)569 that concluded that "...that putrefecation is determined by living ferments".570

Lister was not the only surgeon interested in Pasteur's research.571 Thomas Spencer Wells, surgeon to Queen Victoria, had emphasised the significance of Pasteur's work at a meeting of the British Medical Association in 1864,572 stating "[By] applying the knowledge for which we are indebted to Pasteur of the presence in the atmosphere of organic germs ... it is easy to understand that some germs find their most appropriate nutriment in the secretions from wounds, or in pus, and that they so modify it as to convert it into a poison when absorbed". However, Wells did not have an experiment to demonstrate germ theory and was unable to develop the techniques to put it into practice.573

Lister's colleaguesLouis Pasteur before 1895Thomas Anderson c. 1870Thomas Spencer Wells

Discovery

The serendipitous discovery of Pasteur's work at a time when he was struggling to control post-surgical infections574 provided a simple explanation for a problem he had long experienced.575576 He was now convinced that infection and suppuration of wounds must be due to entry into the wound of minute living airborne creatures.577 He recognised that contamination was the vector for infection, realising from the first that the surgeon's hands, dressings and instruments would also be contaminated.578 However, Pasteur's work confirmed the view Lister had always expressed that contamination came from the air. Lister did not realise the vast and diverse amount of microbial life.579 As Lister's work at that time derived directly from Pasteur's, Lister probably thought that wound infection was due to a single organism. He had no concept, nor indeed did anybody else, of the vast number of types of germs.580 Reading the papers did spur him to determine how the hands, dressings and instruments he used could be rid of these ubiquitous organisms and how the wound could be cleared of them.581

Pasteur suggested three methods to eliminate microorganisms: filtration, exposure to heat, or exposure to chemical solutions. Lister was particularly interested in the efficacy of filtration and repeated many of Pasteur's experiments in modified form for instruction in his class,582 but eventually excluded the first two techniques as not applicable for the treatment of wounds.583

Lister confirmed Pasteur's conclusions with his own experiments and decided to use his findings to develop antiseptic techniques for wounds.584

Carbolic acid

In 1834, Friedlieb Ferdinand Runge discovered the germicide phenol, then known as carbolic acid, which he derived in an impure form from coal tar.585 At that time, there was uncertainty as to the relationship of creosote – a chemical that had been used as a preservative on the wood used for railway sleeper and ships to protect the wood from rotting – and carbolic acid.586 Upon hearing that creosote had been used for treating sewage587 in Carlisle, Lister obtained a sample from Anderson.588 Known as "German creosote", it was a thick, smelly tarry substance.589

Antiseptic system 1865–1867

History

Hospitalism

Main article: History of surgery

The history of antiseptic surgery in the years before 1847, was preventing or treating infection in accidental wounds, often received in battle.590

1860's surgery and pathological theory

In the 1860s, Lister's assumptions about surgery and theory of pathology were similar to those of his contemporaries.591

Early experiments

In early March 1865, Lister conducted his first experiment using the acid on a patient whose wrist was being excised due to caries.592 Although he carefully washed the wound, it became infected and the experiment was a failure.593

On 21 March 1865, Lister began his second experiment with carbolic acid on a 22-year-old patient named Neil Kelly who had a severe compound fracture of the leg.594 His treatment consisted of cleaning the wound of all blood clots and then applying the undiluted carbolic acid by the use of forceps across the whole wound. A piece of lint impregnated in the acid was then laid on the leg, overlapping the wound and fixed by an adhesive plaster. A thin metal sheet made of tin or lead and sterilized by the acid was over the lint, to prevent the antiseptic from evaporating. This was further fixed with adhesive plaster and packing was used between the limb and the splints for the purpose of soaking up any blood or discharges. A crust formed that was not removed except to apply a new antiseptic.595 While the treatment possessed many of the essential characteristics of the antiseptic dressings that Lister would subsequently introduce, it failed and suppuration began to occur,596 leading to the death of the patient. Lister blamed himself and noted that the treatment "..proved unsuccessful, in consequence, as I now believe, of improper management".597

Antiseptic treatment and dressings

The essential part of the wound treatment was not the application of strong carbolic acid to the wound, although that required careful management to ensure the wound was sterilised, but designing the dressing in such a manner to stop the ingress of airborne infection.598 This was often misunderstood, even when he was explaining the procedure to fellow doctors at Glasgow who were celebrating him as humanity's benefactor, and it caused him considerable irritation and unhappiness later in life.599 They were confused by the initial application of the acid and this led to the claim that Lister was advocating for the use of carbolic acid to prevent suppuration.600

The disadvantages of the first primitive dressings of lint soaked in carbolic acid were soon apparent.601 The German creosote was also far from ideal, as it irritated the skin, causing ulceration and then suppuration602 that occasionally resulted in tissue necrosis. It was also almost insoluble in water.603 Lister began to look for another source of phenol. Lister discovered604 that Frederick Crace Calvert, an honorary chemistry professor from the Royal Manchester Institution was manufacturing small quantities of phenol at a much finer purity and managed to obtain some.605 The phenol was in the form of small white crystals which liquified at 80 °F (27 °C)606 and were readily soluble in a ratio of 1:20 parts of water and to any extent soluble in oil.607 The watery solution could be used in a lotion of any strength608 and be used for disinfection of wounds while the solution in oil that served as a reservoir of antiseptic seemed likely to provide a suitable dressing.609 Lister began to experiment with the phenol and produced a new dressing made of a putty that consisted of carbonate of lime mixed with phenol mixed with boiled linseed oil in a ratio of 1:4 or 1:6.610

After two failures, Lister had no clear experimental design611 to test the efficacy of carbolic acid.612 At that point he decided to only experiment on patients with compound fractures, i.e. open wounds where the fractured bone breaks through the skin, leading to extensive loss of blood.613 In 1865, industrial accidents often led to the patient being thrown to the ground, leading to dirt entering the wound and a risk of deep infection.614 By the time the patient saw a surgeon several hours later, suppuration had invariably set in.615 In 1865, amputation was the standard treatment for compound fractures. Lister reasoned that he could experiment on the patient and if the treatment failed, perform the amputation to remove the limb and save the patient's life.616 He believed this experimental model was both ethically and medically ideal.617

James Greenlees

On 12 August 1865, Lister achieved success for the first time when he used the crude oily618 full-strength carbolic acid to disinfect a compound fracture.619620 He applied a piece of lint dipped in carbolic acid solution onto the wound of an 11-year-old boy, James Greenlees, who sustained a compound fracture after a cart wheel passed over his left leg.621 After washing the wound with carbolic acid dissolved in linseed oil, he applied a dressing of putty mixed with the acid widely over the wound and placed a sheet of tin to cover the wound and protect it.622 The putty ensured that the acid did not wash out of the wound in blood or lymph fluid.623 He splinted the leg and bandaged it to hold the lot in place.624 After four days, he renewed the pad and discovered that no infection had developed.625 He again dressed it and left it for five days. When he removed the second dressing, he found the skin around the wound was burnt and applied a dressing of gauze soaked in a combination of 5% to 10% acid and olive oil for a further four days. He then applied a water dressing to the wound until it completely healed.626 After slightly over six weeks, Lister discovered that the boy's bones had fused back together without suppuration.627 Confident that carbolic acid was the antiseptic that he had been looking for, Lister treated patient after patient at the Royal Infimary in the following months,628 improving both the wound dressing design and the operating treatment.

During the summer, the Listers never strayed far from Glasgow as he was still monitoring Greenlees.629 In the same month, he treated two ulcers. Both sores were washed with an acid in oil solution and one was covered with an oiled paper coated with spirit varnish and the second with gutta-percha covered with a water dressing. In both cases the dressing failed and he swapped them for a water dressing covered with cotton.630 On 11 September 1865, Lister treated the second patient with the acid, Patrick F., a labourer with a compound fracture of the thigh.631 After the thigh was splinted, the small wound was dressed using lint dipped in carbolic acid and covered in oil paper.632 After 16 days, the patient had an excellent prognosis.633 On 22 September, the Listers decided to take short holiday to Upton and the patient was left with his house surgeon, John Macfee. However, the treatment failed and the limb was amputated after gangrene developed in the wound.634 When he wrote up his seminal paper, Lister considered the wound size too small to have effectively tested the efficacy of the acid, but he was happy with the outcome.635 At Christmas 1865, the Lister joined the Symes in Edinburgh. It was eight months before Lister treated another compound fracture. On 22 January 1866 he treated John Austin, a shipwreck survivor with a wound in the leg that had developed into an ulcer.636 He washed the wound in 20:1 oil-to-acid solution and dressed it with a lint bandage dipped in the solution covered with plaster of paris.637

Improved dressing

On 19 May 1866, the first patient to use the improved method638 presented at Lister's accident ward with a compound fracture with extensive swelling and bruising.639 The patient was John Hainy, a 21-year-old casting moulder in an iron foundry, who had been supervising a crane when a chain broke and a metal box, containing a sand mould weighing 12 hundredweight or 1,344 pounds (609.6 kg), fell from a height of four feet and landed obliquely on his left leg.640 Both leg bones were broken and a wound measuring 1.5 by 0.75 inches (38 by 19 mm) had bled profusely into the muscles and tissue of the leg. A secondary complication had occurred when air bubbles had mixed with the blood when the man was moved to the hospital.641 The normal treatment would have been amputation, but Lister decided to treat the wound with phenol.642 He squeezed the leg to remove as much air and blood as possible, then placed a piece of lint soaked in carbolic acid on the wound and covered it with tin foil.643 A bloody crust formed over the wound, consisting of a scab free of bacteria.644 Lister saw for the first time how the scab was gradually converted into living tissue, even when new carbolic acid was being applied - something entirely new.645 Unfortunately Hainy developed bed sores that became gangrenous. These were treated with nitric acid to remove the necrotic flesh and carbolic acid to sterilize the wounds.646 Hainy survived the injury. On 27 May, Lister wrote to his father expressing intense satisfaction, stating "I tried the application of carbolic acid to the wound, to prevent decomposition of the blood and to prevent the fearful mischief of suppuration. It is now eight days since the accident and patient has been going exactly as though the fracture were a simple one." Two weeks later another letter followed, reporting "The great swelling has almost entirely subsided, and the limb is becoming firm".647 On 11 June, he wrote a further letter to his father where he describes compound fractures as "no longer a case of uncertainty" and his decision to publish the results.648649 On 7 August 1866, Hainy was released from hospital.650

Refined dressing

Lister continued to refine the dressing and perfect the antiseptic treatment on several other compound fracture and patients with abcesses. He would often spend long nights experimenting in his home laboratory.651 He searched for a material that could be placed over the wound and under the carbolic acid, that would serve to protect the wound from the irritating effects of the acid and stop the ingress of microbes but enable bodily secretions to escape.652 He eventually settled on the use of oiled silk sold under the "Green oiled silk protective" brand.653 The silk surface was painted with one part dextrin, two parts of powdered starch and 16 parts of watery acid in a 20-1 water-acid solution, to ensure a thorough wetting.654655 The sterile silk dressing was an effective barrier between the acid and the tissue.656 He described the new treatment as "An antiseptic to exclude putrefaction with a protective to exclude the atmosphere will by their joint action, keep the wound from abnormal stimulus".657

In July 1866, while he continued to treat compound fracture cases, he applied for a vacant surgeoncy position at the University College London.658 It was an attractive position as a came with guaranteed post at University College Hospital.659 He approached Lord Henry Brougham and prepared a testimonial that included a short description of the antiseptic system,660661 which was the first formal description of his work.662 However, he lost the election.663

Abscess treatment

On 7 November 1866, Lister began using his technique on abscesses, when he successfully treated 12-year old Mary Phillips.664 On 17 March 1867, he treated a 5-year old boy who had a disease of the spine that had developed an large abscess between the umbilicus to the middle of the thigh.665 Known as psoas abscesses, they were often as result of complication from tuberculosis, where pus collects in the muscles within the abdominable cavity.666 They tended to grow very large but the relationship between underlying infection in the bone caused by the tuberculosis and the abscess was not understood.667 The treatment he developed consisted of draining the abscess, placing a piece of lint soaked with carbolic acid in the incision and applying a dressing consisting of layer of the putty then covered with tinfoil.668 The dressing was changed daily with the lint left in place. Eventually the lint was removed after several days, leaving a scar.669 In a letter to his father he stated "...cases of abscess treated in this way is so beautifully in harmony with the theory of the whole subject of suppuration, and besides the treatment is now rendered so simple and easy for any one to put in practice, that it really charms me".670

On a new method of treating compound fracture, abscess

In early 1867, Lister began writing the compound fracture case histories of his experiments with carbolic acid in a series of papers, the first to describe his new technique of antiseptics.671 Titled On a New Method of treating Compound Fracture, Abscess, Etc., with Observations on the Conditions of Suppuration.672 the paper was published in The Lancet in five instalments673 with the first appearing on 10 March 1867.674 and the last part on abscesses added in July 1867. The paper was divided into a main section dealing with compound fractures, and a short note on the treatment of abscesses.675

Lister's theory of inflammation provided the conceptual structure of the article.676 He stated that the inflammation that appeared immediately after an injury was both necessary and dangerous. It was a precursor to healing, but the fluids which flowed into the wound were akin to dead tissue. Inflammation could trigger putrefaction.677 Lister described tissues healing by granulation, which he believed was the likely outcome in wounds in compound fractures. Lister believed that cells of granulated tissue were remarkably active and that since they were alive, they were immune to putrefaction and also to secondary inflammation, as they lacked sensory nerves.678 Airborne putrefaction, "a danger that was underrated", was proven by the scabs which appeared to protect small wounds as they healed.679 Lister then explained how often it appeared in less than 24 hours and had an associated smell. He described the source of putrefaction and how the "raw surface" of the wound could putrify before the granulations formed or the liquids on the surface of the granulations putrified. The liquids were extremely acrid and acted on the sensory nerves to initiate indirect inflammation and fever. This led to increased cell turnover and cellular death, increasing the quantity of putrescent material in the wound. Sloughs were produced that resulted in suppuration.680 In the next section, Lister made his most famous declaration, namely that the decomposition of organic tissue was not caused by the gaseous components in the atmosphere but "minute particles suspended in [the air], which are the germs of various low forms of life, long since revealed by the microscope, and regarded as merely accidental concomitants of putrescence" and had been identified by Pasteur as the "essential cause" of putrefaction.681 He described germs as working in the same manner as yeast converts sugar to alcohol.682 Lister's germs were scavengers who lived on dead tissue. He did not see them as parasites on living tissue. In that respect, Lister's paper is open to many interpretations, but in the context of wounds, he believed that living tissue could resist germs. He never made the distinction as to whether germs were living beings for example in erysipelas, that entered the body or were a chemical agent.683

In the rest of the paper, Lister described using carbolic acid, and how the acid formed a dense crust protecting the wound from the ingress of germs. He then described the detailed case histories of 11 patients.684 Healing by granulation occurred in all cases except 7,10, and 11, which did not suppurate. Cases 1 and 9 did suppurate. Lister did not regard pus as significant, as it was not associated with inflammation or change in putrefaction. In essence, he had attained healing by granulation without inflammation in compound fracture cases. He believed that the elimination of suppuration was not a desirable therapeutic outcome, as a small amount of suppuration on a healthy granulation was not a cause for alarm.685

Medical discourse

During his life, Lister never wrote any books and was exhausted by the process of writing. He considered the meaning of each individual word, which would meant writing a book both extremely time-consuming and a burden.686 An example of Listers poor communication was placing the reason for his antiseptic treatment at the end of the first antiseptic paper, instead of in the first paper.687 Foremost amongst his biographers to examine Listers writing skills was Joseph Fisher, who pointed to his flatness of expression and his inability to state the obvious, i.e. that he was seeking to prevent putrefaction.688 Fisher wondered if it was simple "stylistic ham-handedness", a statement examined by Connor and Connor in 2008.689 Lister used the Greek word antiseptic to describe his new technique. This 1752 term was widely known in the medical community and meant the cleaning the wound of dead flesh with an antiseptic fluid. Lister's use resulted in confusion for his readers and slowed the adoption of the new technique.690 Medical historian Michael Worboys stated that his surgical contemporaries reported that "translating his words into action" was difficult.691 Connor and Connor analysed Lister's public and private written and spoken communication to determine if this was true.692 They concluded that Lister was not bad at writing and this was seen in his private letters to his father, describing the textual content as "clear, concise, informative and concrete".693 Although Lister understood the need to remain neutral and objective in his public communication, he struggled to find a suitable ethos that would clearly convey his ideas and that resulted in his writing sounding awkward and unnatural.694 Sir Charles Scott Sherrington attributed Lister's "sobriety of expression" and "self-restrained statements" to his Quaker faith.695

In 2013, Worboys examined Lister writing from three different perspectives. what he termed the "performative aspect".696

Carcinoma of the breast

In July 1867, Lister discovered that his sister Isabella Pim had breast cancer.697 Pim had visited Paget and Syme to seek treatment but had such an extensive carcinoma that both surgeons advised against operating.698 Lister made the difficult decision to perform a radical mastectomy. He consulted Syme in Edinburgh and rehearsed the operation on a dead body. The recovery went smoothly and although there was some suppuration in the wound, Lister's use of antiseptics prevented putrefaction.699 The next day he wrote to his father, "I may say the operation was done at least as well as if she was not my sister. But I do not wish to do such a thing again."700 Pim lived for another three years before dying of liver metastasis701 on 9 August 1870.702

Antiseptic principle of the practice of surgery

Within a few days of the publishing of the last part of the previous paper, Syme asked Lister to attend the British Medical Association meeting in Dublin on 9 August 1867.703 Lister had some difficulty preparing a new paper, the seminal "On the Antiseptic Principle in the Practice of Surgery-*" Lister's second paper on antiseptic surgery.704 It was later published in the British Medical Journal on 21 September 1867.705

Lister claimed that based on experiments on inflammation, the essential cause of suppuration in wounds was decomposition.706 Several aspects of this claim need to be examined. Firstly, it was specific to wounds, as Lister had other views about suppuration elsewhere on the body. Secondly, he stipulated that decomposition was the "essential" cause of suppuration, i.e. not the only cause. Thirdly, decomposition was the cause of pus in wounds.707 Lister's pronouncement is best described as that he had discovered that the only important cause of suppuration in inflamed wounds is decomposition. Lister was specifically referring to the pathology of pus formation in inflamed tissue, the essential cause of harm in the practice of surgery.708 His appeal to the reader, in essence, to surgical consensus, was: "To prevent the occurrence of suppuration, with all its attendant risks, was an object manifestly desirable", and refers to the surgeon's dread of pus appearing in an inflamed wound.709 Lister then made the wholly inaccurate statement that "...oxygen, which was universally regarded as the agent by which putrefaction was effected" compared to other sources.710 Lister introduced the work of Pasteur, claiming that decomposition might be avoided by using a dressing that could destroy the minute organisms in the wound.711 Lister decided to formulate his new surgical technique into a general principle.712 He termed it the "antiseptic principle", thus linking its nomenclature to carbolic acid.713 His principle was that all the local inflammatory mischief and general febrile disturbance which follow severe injuries are due to the irritation, and the reason for this was the carbolic acid induced suppuration but prevented decomposition, which was contrary to normal surgical treatment that saw suppuration as an indication that something was wrong, in Lister's case essentially that the antiseptic treatment had failed.[325] influence of decomposing blood or sloughs.714715 He stating a "great principle" – not that decomposition was the cause of disease in wounds, but that it was the only cause.716

The paper instructed surgeons to continue treatment even when suppuration appeared.717 The reason for this was the carbolic acid-induced suppuration but prevented decomposition, which was contrary to normal surgical treatment, which saw suppuration as an indication that something was wrong, in Lister's case essentially that the antiseptic treatment had failed.718 He noted that he felt it necessary to affirm on "pathological principles" that granulation tissue had no inherent tendency to form pus but only did so when "subjected to a preternatural tendency". He explained that carbolic acid and decomposing substances were similar, i.e., both caused suppuration by a chemical process but carbolic acid only acted on the surface of the tissue to which it was applied, but decomposition is a "self-propagating and self-aggravating poison". Decomposing tissue was a breeding ground for more decomposition that led to putrefaction in the tissue surrounding it.719

Lister argued that the pus formed by carbolic acid was acceptable as long as it was not accompanied by inflammation. In this respect, Lister's approach to normal or abnormal healing by granulation was the same as the average surgeon of the period: that healthy healing did not occur when inflammation was present.720

Lister paid particular attention to putrefaction. The last part of the paper stating that decomposing wounds were the cause of disease in hospitals, which was not an uncommon belief amongst the surgical community.721 He described how the two large wards where he offered treatment were the unhealthiest in Glasgow and how since the application of antiseptics, "wounds and abscesses no longer poison the atmosphere with putrid exhalations" and the wards completely changed their character.722 Not a single instance of pyaemia, hospital gangrene, or erysipelas had occurred in them since the new regime of antiseptics had begun.723 However, Lister did not explain how the "putrid exhalations" led to fever.724

Illustrations of the antiseptic system of treatment in surgery

On 21 September 1867, Lister published a new paper, "Illustrations of the Antiseptic System of Treatment in Surgery", in The Lancet,725 his third paper on antisepsis. This paper was supposed be the first in a new series with the next paper to be on wounds with simple incisions but it never appeared.726

The paper summarised his earlier claims and added further observations on the nature of putrefaction.727 He stated that the "character of the decomposition in a given fermentable substance is determined by the nature of the organism that develops in it".728 He suggested that the cause of fermentation in food was yeasts and putrefaction was possibly caused Vibrios (a type of bacteria).729 At the end of the paper, he stated that on the basis of his new antiseptic theory "a really trustworthy treatment for compound fractures and other severe contused wounds has been established for the first time, so far as I am aware, in the history of surgery".730

First reception of antisepsis

Although Lister was honoured in later life, his ideas about the transmission of infection and the use of antiseptics were widely criticised in his early career.731 On 24 August 1867, within a month of Lister's publishing his first paper on antiseptics, the editor of The Lancet, Lister's nemesis James G. Wakley, wrote an editorial crediting Pasteur for Lister's research and invited physicians to investigate Lister's claims and report their findings to the journal.732

Simpson's attack

On 21 September 1867, Scottish obstetrician James Young Simpson, professor of medicine and midwifery at Edinburgh University and discoverer of chloroform, published an editorial that attacked Lister in the Edinburgh Daily Review, written under the pen name "Chirurgicus", a common practice to signal a personal attack.733 Simpson's motive was that he was trying to convince the medical community of the efficacy of his acupressure technique, which used needles to halt arterial haemorrhage, counter to Lister's use of ligatures.734 The editorial letter was the first of many and began a tit-for-tat argument in the press over months and eventually led to the acceptance of antisepsis.

Simpson claimed that Lister's prior article had copied a continental practice735 and accused him of plagiarising the work of French doctor and pharmacist Jules Lemaire.736 Lemaire had described carbolic acid as a constituent of coal tar in 1860737 in "Saponinated coal tar"738 and after a long series of investigations739 had followed up with an 1863 book, "De l'acide phénique, de son action sur les végétaux, les animaux, les ferments, les venins, les virus, les miasmes et de ses applications à l'industrie, à l'hygiène, aux sciences anatomiques et à la thérapeutique" (Carbolic acid, its action on plants, animals, ferments, venoms, viruses, miasmas and its applications to industry, hygiene, anatomical sciences and therapy) with the second edition in 1865, where he described the antiseptic power of carbolic acid.740741742 While Lemaire believed in the germ theory and realised the causes of putrefaction, he made no attempt to develop a process to exclude them from the wound.743

On 5 October 1867, Lister gave a robust reply to Simpson in a letter "On the Use of Carbolic Acid" to The Lancet, denying that he had heard of Lemaire's work and arguing that that work had made little impact on the medical profession.744745 Lister went on to defend his work, stating:

"For my own part, I may say that, of all the gentlemen from Great Britain and both continents who have recently visited Glasgow, not one has ever expressed the slightest doubt that the system in question was entirely new; the novelty, I may remark, being, not the surgical use of carbolic acid (which I never claimed), but the methods of its employment with the view of protecting the reparatory processes from disturbance by external agency."

He unsuccessfully searched all the Glasgow libraries for Lemaires work746 before finally discovering a copy in the library of Edinburgh University.747 On 19 October, Lister wrote a follow-up letter to The Lancet748 and stated he did not claim to be the first physician to use carbolic acid and that he chose the acid due to its strength as an antiseptic. He also included a letter of support from a Carlisle medical student, Phillip Hair, who had studied in Paris. Hair stated he had seen no treatments there that were as effective as Lister's.749 Lister's response angered Simpson and two weeks later on 2 November 1867 he published a bitter reply: "Carbolic acid and its compounds in surgery" in, The Lancet under his own name.750 Simpson reiterated his previous claims about Lemaire's and others' prior use of the acid, mentioning James Spence, who had used the acid to wash amputations, but had abandoned its use.751 He cited a report by Sampson Gamgee who visited Paris and reported that surgeons were using a solution of 100:1 of water to acid, while Lister recommended 40:1.752 Simpson exposed his true motives when he compared his preferred technique of acupressure to Lister's use of ligatures. He used the work of William Pirrie, professor of surgery at Aberdeen University, who had used acupressure to stop pus formation during breast cancer operations, to illustrate his point, that there had been no deaths from pyaemia at the hospital, compared to the many deaths in Glasgow and Edinburgh.753 Simpson was acutely embarrassed when Pirrie replied a week later in The Lancet in a small article titled "On the Use of Carbolic Acid in Burns",754 recommending its use for burn injuries and believing it proved effective in other treatments. Lister replied with a short note on 9 November755 to ask the reader to: "to judge for themselves how far the present attack admits of justification, promising to publish additional articles on his antiseptic technique".756

First response to antiseptic surgeryWakley, the Lancet editor who invited responses to Lister's papersYoung became Lister's nemesis, to promote his accupressure technique.Pirrie described using the acid for burn treatment.Sampson Gamgee documented the early use of carbolic acid in Paris.

In 1869, at the meetings of the British Association at Leeds, Lister's ideas were mocked; and again, in 1873, the medical journal The Lancet warned the entire medical profession against his progressive ideas.757 However, Lister did have some supporters, including Marcus Beck, a consultant surgeon at University College Hospital, who not only practised Lister's antiseptic technique, but included it in the next edition of one of the main surgical textbooks of the time.758759

Sterility experiment

In October 1867, Lister repeated a modified form of Pasteur's experiment, originally devised by French chemist Chevreul, to support his germ theory and disprove the theory of spontaneous generation.760 Lister poured urine into four glass flasks, then washed the necks to remove any urine and modified three of them, extending and drawing their necks into a narrow tube bent at an acute angle.761 The fourth's neck was cut short and left vertical, but with a reduced diameter, smaller than the others' necks. The flasks were then boiled and when the heat was withdrawn, air was allowed to rush into the flask to replace the condensed steam. The flasks were then left undisturbed in the same room, the necks open to the air.762 Within four days a vegetative mould appeared in the fourth flask while the other three flasks remained clear.763 In November, he began using the flasks in his class.764 His dresser John Rudd Leeson described how Lister took the three flasks to London on their laps in a specially reserved first-class cabin, to ensure they survived the journey.765

Sterility experiment to disprove the theory of spontaneous generationGlass flask used in the experimentGlass flask containing urineLouis Pasteur's pasteurization experiment illustrates the fact that the spoilage of liquid was caused by particles in the air rather than the air itself. Lister sought to duplicate Pasteur's experiments as they important pieces of evidence supporting the germ theory of disease.

The catgut ligature

A practical problem in general surgey that Lister researched and development was in the use of ligatures that were used to tie large vessels during amputation.766 It had been known for years that gunshot bullets, i.e smooth metallic objects could remain the body without supporation767 but supparation would occur in silk or thread ligatures, which resulted in the ends being left outside the body to enable its removal. However, that left a path open to germs to enter the body along the material and it also risked secondary hemorrhage when they were removed.768. By late 1867, he understood that ligatures were sources of irritation.769 He had also noticed how a piece of dead bone in a compound fracture case had slowly become alive as new blood vessels had grown into it.770 He surmised that he could find a material that could be absorbed into the body, reducing the ingress of germs.771 He initially took the standard silk thread and impregnated it with carbolic acid.772 On 12 December 1867, in the first of a series of experiments,773 he tested the new ligature by tying the carotid artery of a horse. When the horse died six weeks later (of natural causes) it was dissected and he found dense fibrous tissue had grown over the ligature.774 But he noticed the silk was being absorbed rather slowly.775

On 2 February 1868, in a letter to his father he reported using the new ligature on private patient who was being operated on for a leg aneurism.776 The patient recovered completely. On 5 February he wrote to his father, expressing his profound excitement at the patients recovery.777 However, the lady died 10 months later of another aneurism due to vascular disease.778 During the dissection, Lister found that most of the ligature had been absorbed but found a tiny blob of thick pus on the remaining piece, that led him to think an abcess could have formed.779 He began looking for another material and settled on catgut.780781 On 31 December 1868, while staying at Upon for Christmas, Lister tested the carbolised catgut on an calf, running the experiment in his fathers museum.782 He again tied the carotid artery. After a month, the calf was dissected.783

On 3 April 1869, he published "Observations on Ligature of Arteries on the Antiseptic System" in The Lancet.784.

Edinburgh appointment

Lister left Glasgow University in October 1869785 and was succeeded by George Husband Baird MacLeod.786 Lister returned to Edinburgh as successor to Syme as professor of surgery at the University of Edinburgh and continued to develop improved methods of antisepsis and asepsis. Amongst those he worked with there, was the senior apothecary and later MD, Alexander Gunn.787

Edinburgh 1869–1877

In Edinburgh, his primary objectives were to perfect the design of his dressings, improve the reliability of antiseptics and apply his technique to an ever wider class of operations. He selected cases of the repair of bone deformities and rewiring of fractures where the union had malformed while healing.788

In 1870, Lister published "On the Effects of the Antiseptic System of Treatment upon the Salubrity of a Surgical Hospital".

First experimentalist

The first experimentalist surgeon to question the validity of the airborne microorganisms hypothesis was Edinburgh surgeon and professor of medicine John Hughes Bennett.789 In a January 1868 lecture for the Edinburgh Medical Journal, Bennett advanced The Atmospheric Germ Theory,790 agreeing with the theories of Félix Archimède Pouchet, professor of natural history at the University of Rouen, who believed in spontaneous generation of life.791 Bennet described his own theory of molecular degeneration to explain how microorganisms transformed old tissue into new tissue by the action of molecules.792 Bennett taught that molecules rather than cells were the foundational building blocks of tissue and that microorganisms could be spontaneously created from different combinations of molecules. In his view, each molecule had a specific function, i.e. certain molecules were destructive to tissue, while others constructed tissue.793

Bennett believed that diseases developed from the physical properties of the air, such as its density or changes in temperature.794 Bennett believed that the germs that Pasteur captured could not be identified as organic organisms.795 The components of this dust were also found in minerals and they were either lint, debris from clothing, vegetable matter or pieces of seeds.796 Bennett particularly disagreed about temperature. Pasteur stated that germs died when heated to 30 degrees above boiling, and also from extreme cold. In the lecture, he referred to Pouchet's experiments duplicating Pasteur's, and refuted Pasteur's conclusions.797 Bennet did not realise that Pasteur had proved his theory by both isolating the germs and stopping them from reappearing. In his experiments, Bennett reported that he "proved" that germs generate spontaneously, so therefore one could never create a germ-free environment.798

The experimentalistsBennet believed in the spontaneous generation of life.Pouchet believed in the spontaneous generation of life.

It was likely that Hughes Bennett never adequately sterilized his experimental apparatus correctly.799 On 8 November 1868, Lister gave a lecture on germ theory, where he elaborated on the origin of germs, as a rebuttal of Bennett's theory.800

Lister's meticulous nature became ever more apparent in his casebooks for wards 4 and 5 at the infirmary.801

Effects of the antiseptic system of treatment upon the salubrity of a surgical hospital

On 14 January 1871, Lister published his first details of Gauze and Spray in the British Medical Journal.802

In 1872 he was elected a member of the Aesculapian Club.803

Sprays

Therefore, Lister tested the results of spraying instruments, surgical incisions, and dressings with a solution of carbolic acid. Lister found that the solution swabbed on wounds remarkably reduced the incidence of gangrene.804

London 1877–1900

On 10 February 1877, the Scottish surgeon Sir William Fergusson, Chair of Systematic Surgery at King's College Hospital, died.805 On 18 February, in reply to a tentative approach from a representative of Kings College, Lister stated that he would be willing to accept the chair806 if he could radically reform the teaching there.807 There was no doubt that Lister's mission was both evangelical and apostolic and this was his true purpose in moving to London.808

British surgeon John Wood, originally next in line, was elected to the chair.809 Wood was hostile to Lister obtaining the chair.810 On 8 March 1877, in a private letter to an associate, Lister contrasted their differing teaching methods and stated in no uncertain terms his opinion of Fergusson, "The mere fact of Fergusson having held the clinical chair is surely a matter of no great moment".811 In a comment to another colleague, Lister stated that his goal in taking the appointment was "the thorough working of the antiseptic system with a view to its diffusion in the Metropolis".812 At a memorial held by his students to persuade him to remain, Lister criticised London teaching. His impromptu speech was heard by a reporter who ensured that it was published in the London and Edinburgh newspapers.813 This jeopardised Lister's position, as word reached the governing council at King's College, who awarded the chair to John Wood a few weeks later.814

However, negotiations were renewed in May and he was finally elected on 18 June 1877 to a newly created Chair of Clinical Surgery.815 The second Clinical Surgery Chair was created specifically for Lister because the hospital feared the negative publicity that would have resulted had Lister not been elected.816 Lister remained at King's College Hospital for sixteen years before retiring in 1893 following the death of his wife.817

Moving to Regents Park

On 11 September 1877, Joseph and Aggie moved to London818 and found a house at 12 Park Crescent in Regent's Park.819 Lister began teaching on 1 October.820 The hospital made attendance at Lister's lectures mandatory for all students.821 Attendance was small, compared to the four hundred students who regularly attended his classes in Edinburgh.822 Lister's conditions of employment were met, but he was only provided with 24 beds, instead of the 60 beds that he was used to in Edinburgh.823 Lister stipulated that he should be able to bring from Edinburgh four people who would constitute the core of his new staff at the hospital.824 These were Watson Cheyne who became his assistant surgeon, John Stewart, an anatomical artist and senior assistant, and W. H. Dobie and James Altham Lister's dressers (surgical assistants who dressed wounds).825 There was considerable friction at Lister's first lecture, both from students who heckled him826 and staff. Even the nurses were hostile.827 This was clearly illustrated in October 1877828 when a patient, Lizzie Thomas, who travelled from the Edinburgh Royal Infirmary to be treated for a Psoas abscess, was not admitted due to not having the correct paperwork.829 Lister could hardly believe that such a lack of sympathy from imperious nurses could exist.830 More so, such a state of mind was a real danger to his patients, because his system depended on loyal staff to carry out the preparations for antiseptic surgery.831

Introductory address

On 1 October 1877, Lister held the customary introductory address. His inaugural lecture in London concerned "The nature of fermentation".832 Lister described the fermentation of milk and explained how putrefaction was caused by fermentation of blood833 and tried to prove that all fermentation was due to microorganisms. To demonstrate, he used a series of test tubes containing milk, loosely covered with glass caps.834 Although air had entered the test tubes and the milk had not decomposed, demonstrating that air was responsible for fermentation.835 The experiment had two conclusions, first that unboiled milk had no tendency to ferment and secondly that an organism that Lister had isolated,836 Bacterium lactis was the cause of lactic acid fermentation.837

The address was badly received.838 In defence, John Stewart described it as: "a brilliant and most hopeful beginning of what we regarded as a campaign in the enemy's country... There seemed to be a colossal apathy, an inconceivable indifference to the light which, to our minds, shone so brightly, a monstrous inertia to the force of new ideas."839

Medical items at Lister's inaugural lectureTest tubes containing milk. Lister was confident in saying that milk from the cow was not inherently fermentative.

Wiring of fractured patellas

In October 1877, Lister performed an operation on a patient, Francis Smith, that was not considered life-threatening.840841 The open operation on a fractured patella, in front of 200 students, involved wiring the two fragments together842 and was likely the first time a healthy knee-joint was ever opened.843

In 1881 Lister was elected President of the Clinical Society of London.844

In October 1883, St Clair Thomson gathered together and examined Lister's first seven knee surgery patients at the Medical Society of London meeting.845

He also developed a method of repairing kneecaps with metal wire and improved mastectomy technique. He also became known for being the first surgeon to use catgut ligatures, sutures and rubber drains, and developed an aortic tourniquet.846847 He introduced a diluted spray of carbolic acid combined for surgical use. However he abandoned carbolic acid sprays in the late 1890s after he saw that they provided no beneficial change in the outcomes of the surgeries. The only reported reactions were minor symptoms that did not affect the surgical outcome as a whole, like coughing, irritation of the eye, and minor tissue damage among his patients who were exposed to the carbolic acid sprays during the surgery.848

Reception abroad (1870–1876)

In 1869, Mathias Saxtorph from the University of Copenhagen visited Lister in Glasgow to adopt his methods.849 In July 1870, Saxtorph recognised Lister's technique as being effective in a letter to Lister where he stated:

The Frederick Hospital, to which I am head surgeon is a very old building and I have 150 patients in the surgical wards. Foremerly, there used to be every year several cases of death from pyaemia, sometime, arising from the most trivial injuries. Now, I have had the satisfaction that not a single case of pyaemia has occurred since I came home last year, which result is certainly owing to the introduction of your antiseptic treatment.850

Germany

The first use of Lister's method in Germany was by Karl Thiersch in Leipzig in 1867.851 Thiersch practised Lister's approach since its introduction and never published his results, but did teach it to his students.852 His house surgeon Hermann Georg Joseph tested it on 16 patients with abscesses, with favourable results.853 Joseph wrote a thesis on his results, proving the value of the Lister method, and presented in Leipzig the following year.854 In January 1870, Heinrich Adolf von Bardeleben presented a paper to the Berlin Medical Society that described the results but provided no statistical evaluation of them.855

The adoption of Listerism on the European continent halted during the Franco-Prussian War, but it became the greatest opportunity to advance Lister's ideas.856 At the start of the war, Lister had written a pamphlet known as "A Method of Antiseptic Treatment Applicable To Wounded Soldiers in the Present War" that described a simplified technique of antiseptic that could be used on the battlefield and military hospital.857 The pamphlet was immediately translated into German, but never made a material difference.858

By far the most important advocate for Lister's antiseptic system in Germany was surgeon and osteotomy specialist859 Richard von Volkmann, who taught at the University of Halle.860861 In August 1870, he became surgeon-general during the Franco-Prussian War and was responsible for 12 army hospitals and 1442 beds.862 When he returned to his own hospital in the winter of 1871, he found large numbers of patients with infectious diseases throughout the ward.863 He wrote of the experience:

The mortality after large amputations and complicated fractures grew year by year. In the summer of 1871, during my absence on the battlefield, the clinic was crowded by a large amount of injured. For eight months, in the winter of 1871 to 1872, the numbers of blood poisoning and rose disease victims were so great, that I considered applying for a temporary closure of the facility. Without a morgue, the dead stayed in the cellar beneath the wards

In 1872, Volkmann sent his assistant Max Schede to visit Lister at his clinic, to learn his new techniques.864 Once Schede returned in the autumn of 1872, Volkmann began to use Lister's new techniques.865 On 16 February 1873, in a letter to Theodor Billroth, Volkmann wrote:

since autumn of last year (1872), I have been experimenting with Lister's method... Already, the first trials in the old 'contaminated' house, show wounds healing, uneventful, without fever and pus.866

In April 1874, Volkmann presented a lecture titled: "About antiseptic occlusive bandages and their influence on the healing process of wounds" where he detailed the influence of Lister.867 The lecture became famous in Germany, to such an extent that Lister's antiseptics were established in Germany, faster than in any other developed country. At the German Congress of Surgery, the members were so enthused with the results of Lister's work, that they invited him to visit Germany and see first-hand the results of his work.868 Lister decided to accept the invitation to a continental tour.869

In the spring of 1875, Lister along with Agnes, his sister-in-law and two nieces left Edinburgh.870 The group spent several weeks in a tour that began in Cannes in France, visited several cities in Italy and finished with a four-day visit to Venice.871 The first place in Germany that Lister visited was the "Allgemeines Krankenhaus" (general hospital) in Munich, which was run by Nussbaum.872 A celebratory dinner was held in Munich for Lister, with seventy guests.873 Lister received his most glorious reception in Leipzig, where Karl Thiersch held a banquet for three to four hundred guests.874 Lister then visited Volkmann in Halle before visiting Berlin, where the group was entertained by Heinrich Adolf von Bardeleben, who worked at the Charité hospital and was one of the earliest adopters of antiseptics.875

Later life

In December 1892, Lister attended a celebration of the 70th birthday of Pasteur at the Sorbonne in Paris,876 The theatre, designed to hold 2500 people, was crowded and included the university governing staff, ministers of state, ambassadors, the President of France Sadi Carnot and representatives from the Institut de France.877 Lister, invited to give the address, received a great ovation when he stood up. He spoke of the debt that he and surgery owed to Pasteur.878 In a scene captured later by Jean-André Rixens, Pasteur strode forward and kissed Lister on both cheeks.879 In January 1896, Lister was present when Pasteur's body was laid in his tomb at the Pasteur Institute.880

Joseph Lister acclaims Louis Pasteur at Pasteur's Jubilee, Paris, 1892. Photograph after a painting by Jean-André Rixens

In 1893, four days into a spring holiday in Rapallo, Agnes Lister died from acute pneumonia.881 While still responsible for the wards at Kings College Hospital, Lister's private practice ceased along with an appetite for experimental work. He severely curtailed social gatherings, studying and writing lost appeal for him, and he sank into religious melancholy.882 Lister retired from Kings College Hospital in 1893.883884 Lister was presented with a portrait painted by Scottish artist John Henry Lorimer, in a small presentation, held in recognition of the affection and esteem that felt by his colleagues.885

Despite suffering a stroke, he still came into the public light from time to time. He had for several years been a Surgeon Extraordinary to Queen Victoria, and from March 1900 was appointed the Serjeant Surgeon to the Queen,886 thus becoming the senior surgeon in the Medical Household of the Royal Household of the sovereign. After her death the following year, he was re-appointed as such to her successor, King Edward VII.887

On 24 June 1902, with a 10-day history of appendicitis with a distinct mass on the right lower quadrant, Edward was operated on by Sir Frederick Treves two days before his scheduled coronation.888 Like all internal surgery at the time, the appendectomy needed by the King still posed an extremely high risk of death by post-operational infection, and surgeons did not dare operate without consulting Britain's leading surgical authority.889 Lister obligingly advised them in the latest antiseptic surgical methods (which they followed to the letter), and the King survived, later telling Lister, "I know that if it had not been for you and your work, I wouldn't be sitting here today."890

In 1908, Lister left London to live in the coastal village of Walmer at Park House.891

Death

Lord Lister died on 10 February 1912 at his country home at the age of 84.892 The first part of Lister's funeral was a large public service held at Westminster Abbey, which took place at 1.30 pm on 16 February 1912.893 His body was moved from his house and taken to the Chapel of St. Faith and a wreath of orchids and lilies was placed by the German ambassador Count Paul Wolff Metternich on behalf of the German Emperor Wilhelm II.894 Before the start of the service, Frederick Bridge played the music of Henry Purcell, the funeral march by Chopin and Beethoven's Tres Aequili.895 The body was then placed on a high catafalque, where his Order of Merit, Prussian Pour le Mérite and Grand Cross of the Order of the Dannebrog were placed.896 It was then borne by several pallbearers including John William Strutt, Archibald Primrose, Rupert Guinness, Archibald Geikie, Donald MacAlister, Watson Cheyne, Godlee and Francis Mitchell Caird897 where the catafalque was conveyed to Hampstead Cemetery in London,898 reaching it at 4pm.899 Lister's body was then buried in a plot in the south-east corner of the central chapel, attended by a small group of his family and friends. Many tributes from learned societies all over the world were published in The Times on that day.900 A memorial service was held in St Giles' Cathedral in Edinburgh on the same day.901 Glasgow University held a memorial service in Bute Hall on 15 February 1912.902

A marble medallion of Lister was placed in the north transept of Westminster Abbey, which sits alongside four other noted men of science, Darwin, Stokes, Adams, and Watt.903

Lister's funeral and medallionJoseph Lister, Baron Lister's funeral procession leaving Westminster AbbeyLister's hearse prior to his funeral service at Westminster AbbeyMemorial plaque in marble to Lister by Thomas Brock in 1915

Lister Memorial Fund

Following his death, the Lord Lister Memorial Fund was established by the Royal Society as a public subscription to raise monies for the public good in honour of Lord Lister.904 It led to the founding of the Lister Medal, considered the most prestigious prize that can be awarded to a surgeon.

Awards and honours

On 26 December 1883, Queen Victoria created Lister a baronet, of Park Crescent in the parish of St Marylebone in the county of Middlesex.905

In 1885, he was awarded the Pour le Mérite, the highest Prussian order of merit.906 The order was restricted to 30 living Germans and as many foreigners.907

On 8 February 1897, he was further honoured when Her Majesty raised him to the peerage as Baron Lister, of Lyme Regis in the county of Dorset.908909

In the 1902 Coronation Honours list published on 26 June 1902 (the original day of King Edward VII's coronation),910 Lord Lister was appointed a privy counsellor and one of the original members of the new Order of Merit (OM). He received the order from the King on 8 August 1902,911912 and was sworn a member of the Privy Council at Buckingham Palace on 11 August 1902.913 In December 1902, the King of Denmark bestowed upon Lister the Knight of the Grand Cross of the Order of the Dannebrog,914 an Order of chivalry that gave him more pleasure than any of his later honours.915

Lister's coat of arms, order of chivalry and orders of meritArms of Lord Lister: Ermine, on a fess invected sable three mullets of six points argent in chief a Staff of Aesculapius erect proper with canton of a baronet, Red Hand of UlsterPour le mérite, awarded in 1885Order of merit, awarded in 1902Grand Cross, Order of the Dannebrog, awarded in 1902

Medals

Throughout his life, Lister was awarded a number of medals for his achievements.

In May 1890, Lister was awarded the Cameron Prize for Therapeutics of the University of Edinburgh,916 that included the delivery of a short oration or lecture, that was held at the Synod Hall in Edinburgh.917 In November 1902, Lister was awarded the Copley Medal by the Royal Society "for sustained, outstanding achievements in any field of science".918

Academic societies

Lister was a member of the Royal College of Surgeons of England between 1880 and 1888.

In 1877, Lister was awarded the Cothenius Medal of the German Society of Naturalists.919 In 1886, he was elected vice president of the college, but declined the nomination for office of president, as he wished to devote his remaining time to further research.920 In 1887, Lister presented the Bradshaw lecture with a lecture titled "On the Present Position of Antiseptic Treatment in Surgery".921 In 1897, Lister was awarded the College Gold Medal, their highest honour.922

Lister was elected to the Royal Society in 1860.923 He served as a trustee on the Royal Society council between 1881 and 1883.924 Ten years later, in November 1893 Lister was elected for two years, to the position of foreign secretary of the society, succeeding the Scottish geologist Sir Archibald Geikie.925 In 1895, he was elected president of the Royal Society926 succeeding Lord Kelvin. He held the position until 1900.927

In March 1893, Lister received a telegram from Pasteur, Félix Guyon and Charles Bouchard that informed him he had been elected an associate of the Academie des Sciences.928

Lister was elected an International Honorary Member of the American Academy of Arts and Sciences in 1893, an International Member of the American Philosophical Society in 1897, and an International Member of the United States National Academy of Sciences.929930931

Monuments and legacy

In 1903, the British Institute of Preventive Medicine was renamed Lister Institute of Preventive Medicine in honour of Lister.932 The building, along with another adjacent building, forms what is now the Lister Hospital in Chelsea, which opened in 1985. The building at Glasgow Royal Infirmary which houses the cytopathology, microbiology, and pathology departments was named in Lister's honour to recognise his work at the hospital.933 The Lister Hospital in Stevenage, Hertfordshire is named after him.934

Lister's name is one of 23 people featured on the frieze of the London School of Hygiene & Tropical Medicine935 – although the committee which chose the names to include on the frieze did not provide documentation about why certain names were chosen and others were not.936

Monuments erected in Listers honourLister Building at the Glasgow Royal InfirmaryLister Room, Royal College of Physicians and Surgeons of GlasgowLister Frieze, Polyclinic Umberto I hospital in Rome. The tympanum sculptures show Lister operating.Image of Lister's name on the London School of Hygiene & Tropical Medicine, in Keppel StreetPlaque commemorating Joseph Lister on the facade of the polyclinic in Vienna

Only two British surgeons have public monuments in London, Lister and John Hunter. The statue of Lister, created by Thomas Brock in bronze in 1924, stands at the north end of Portland Place.937 A bronze statue of Lister, mounted on a granite base in Glasgow's Kelvingrove Park, was sculpted by George Henry Paulin in 1924. It sits next to a statue of Lord Kelvin.938

Statues and plaques in Listers honourLord Lister Memorial in Portland Place by Sir Thomas Brock in bronze, 1924Lord Lister memorial in Kelvingrove Parkby by George Henry Paulin in bronze, 1924Plaque at 12 Park Crescent, Regent's Park, LondonPhotogravure plaque, Wellcome Institute, London

The Discovery Expedition of 1901–1904 named the highest point in the Royal Society Range, Antarctica, Mount Lister.939

In 1879 Joseph Lawrence, the American inventor of Listerine antiseptic, developed as a surgical antiseptic but nowadays best known as a mouthwash, named it after Lister.940

Microorganisms named in his honour include the pathogenic Listeria bacterial genus named by J. H. H. Pirie, typified by the food-borne pathogen Listeria monocytogenes, and Listerella slime mould genus first described by Eduard Adolf Wilhelm Jahn in 1906.941

Two postage stamps were issued in September 1965 to honour Lister on the centenary of his antiseptic surgery at the Glasgow Royal Infirmary of Greenlees, the first ever recorded instance of such treatment.942

Other things names in Listers honourMount Lister in the Royal Society Range, AntarcticaListeria bacteria, an intracellular parasite in mammalsLister 1 shilling Centenary Stamp issued on 1 September 1965Listerine Antiseptic Bottle

Reference volumes

The following three books are the earliest reference volumes943 on the antiseptic surgery:

See also

Notes

Citations

Bibliography

Articles (journals and proceedings)

Joseph Lister
Louis Pasteur

Books and monographs

=====Joseph Lister=====https://archive.org/details/listerligaturela0000rese Two quarto volumes of Lister's collected papers, that were prepared by Sir Hector Charles Cameron, Sir W. Watson Cheyne, Rickman J. Godlee, C. J. Martin and Dawson Williams:

Chapters and contributions

  • Lister J (1862). "Amputation". In Holmes T (ed.). System of Surgery. Vol. third. London: Parker, Son and Bourn, West Strand. OCLC 697607903. In four volumes. Operative surgery; diseases of the organs of Special sense, respiration, circulation, locomotion and innervation

Dictionaries and encyclopedias

Lectures and addresses

Letters

Medical registers

Newspapers

Theses

Websites

Wikimedia Commons has media related to Joseph Lister, 1st Baron Lister. Wikisource has original works by or about:Joseph Lister

References

  1. Cartwright 2023. - Cartwright FF (2023). "Joseph Lister". Encyclopædia Britannica. Retrieved 8 February 2018. https://www.britannica.com/biography/Joseph-Lister-Baron-Lister-of-Lyme-Regis

  2. Simmons 2002, pp. 94–99. - Simmons JG (2002). "Joseph Lister Antisepsis and Modern Surgery". Doctors and discoveries: lives that created today's medicine. Boston: Houghton Mifflin. pp. 94–99. ISBN 978-0-618-15276-6. OL 7603987M. https://archive.org/details/doctorsdiscoveri00john

  3. Cartwright 2023. - Cartwright FF (2023). "Joseph Lister". Encyclopædia Britannica. Retrieved 8 February 2018. https://www.britannica.com/biography/Joseph-Lister-Baron-Lister-of-Lyme-Regis

  4. Moynihan 1927. - Moynihan B (9 April 1927). "Lister As A Surgeon". The British Medical Journal. 1 (3457): 656–658. doi:10.1136/bmj.1.3457.656. JSTOR 25323114. PMC 2454878. PMID 20773117. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2454878

  5. Simmons 2002, pp. 94–99. - Simmons JG (2002). "Joseph Lister Antisepsis and Modern Surgery". Doctors and discoveries: lives that created today's medicine. Boston: Houghton Mifflin. pp. 94–99. ISBN 978-0-618-15276-6. OL 7603987M. https://archive.org/details/doctorsdiscoveri00john

  6. Ford 1928. - Ford WW (January 1928). "The Bacteriological Work of Joseph Lister". The Scientific Monthly. 26 (1): 70–75. Bibcode:1928SciMo..26...70F. JSTOR 7951. https://ui.adsabs.harvard.edu/abs/1928SciMo..26...70F

  7. Fermentation was the word Lister used for the putrefactive process of sepsis that we might now describe as wound infection[5] /wiki/Sepsis

  8. Gaw 1999, p. 144. - Gaw JL (1999). ""A Time to Heal": The Diffusion of Listerism in Victorian Britain". Transactions of the American Philosophical Society. 89 (1). Philadelphia: American Philosophical Society: iii–173. doi:10.2307/3185883. JSTOR 3185883. https://doi.org/10.2307%2F3185883

  9. Pitt & Aubin 2012. - Pitt D, Aubin JM (1 September 2012). "Joseph Lister: father of modern surgery". Canadian Journal of Surgery. 55 (5): e8 – e9. doi:10.1503/cjs.007112. ISSN 0008-428X. PMC 3468637. PMID 22992425. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468637

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  11. Cameron 1949, pp. 21–22. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

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  49. Lawrence 2004. - Lawrence C (23 September 2004). "Lister, Joseph, Baron Lister (1827–1912), surgeon and founder of a system of antiseptic surgery". Oxford Dictionary of National Biography. Vol. 1 (online ed.). Oxford University Press. doi:10.1093/ref:odnb/34553. https://doi.org/10.1093%2Fref%3Aodnb%2F34553

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  70. Wangensteen & Wangensteen 1974. - Wangensteen OH, Wangensteen SD (1974). "Lister, His Books, And Evolvement Of His Antiseptic Wound Practices". Bulletin of the History of Medicine. 48 (1): 100–128. JSTOR 44451365. PMID 4608034. https://www.jstor.org/stable/44451365

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  570. Wrench 1913, p. 98. - Wrench GT (1913). Lord Lister; his life and work. London: Fisher Unwin, New York: Frederick A. Stokes Company. OCLC 14798321 – via Cornell University. https://archive.org/details/cu31924012168948/page/n7/mode/2up

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  587. Pitt D, Aubain JM (October 2012). "Joseph Lister: father of modern surgery". Canadian Journal of Surgery. 55 (5): E8–9. doi:10.1503/cjs.007112. PMC 3468637. PMID 22992425. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468637

  588. Gaw 1999, p. 29. - Gaw JL (1999). ""A Time to Heal": The Diffusion of Listerism in Victorian Britain". Transactions of the American Philosophical Society. 89 (1). Philadelphia: American Philosophical Society: iii–173. doi:10.2307/3185883. JSTOR 3185883. https://doi.org/10.2307%2F3185883

  589. Godlee 1924, p. 182. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  590. Cartwright 1968, p. 77. - Cartwright FF (1968). "Antiseptic Surgery". In Poynter FN (ed.). Medicine and science in the 1860s: Proceedings of the Sixth British Congress on the History of Medicine University of Sussex 6–9 September 1967. Publications of the Wellcome Institute of the History of Medicine. Vol. XVI. London: Wellcome Institute of the History of Medicine, Cluneberry Press. OCLC 14498003. https://iiif.wellcomecollection.org/pdf/b20086155

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  595. Godlee 1924, pp. 182–183. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  596. Godlee 1924, pp. 182–183. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  597. Brand 2010. - Brand RA (August 2010). "Biographical Sketch: Baron Joseph Lister, FRCS, 1827-1912". Clinical Orthopaedics & Related Research. 468 (8): 2009–2011. doi:10.1007/s11999-010-1319-3. PMC 2895836. PMID 20364338. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895836

  598. Cameron 1949, p. 63. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  599. Cameron 1949, pp. 62–63. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  600. Cameron 1949, p. 63. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  601. Godlee 1924, p. 183. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  602. Cameron 1949, p. 62. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  603. Godlee 1924, p. 183. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  604. Likely from Anderson[300]

  605. Gaw 1999, p. 29. - Gaw JL (1999). ""A Time to Heal": The Diffusion of Listerism in Victorian Britain". Transactions of the American Philosophical Society. 89 (1). Philadelphia: American Philosophical Society: iii–173. doi:10.2307/3185883. JSTOR 3185883. https://doi.org/10.2307%2F3185883

  606. Gaw 1999, p. 29. - Gaw JL (1999). ""A Time to Heal": The Diffusion of Listerism in Victorian Britain". Transactions of the American Philosophical Society. 89 (1). Philadelphia: American Philosophical Society: iii–173. doi:10.2307/3185883. JSTOR 3185883. https://doi.org/10.2307%2F3185883

  607. Cameron 1949, p. 63. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  608. Cameron 1949, p. 63. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  609. Godlee 1924, p. 183. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  610. Godlee 1924, p. 184. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  611. Fisher 1977, p. 135. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  612. Fitzharris 2018, p. 162. - Fitzharris L (2018). The butchering art: Joseph Lister's quest to transform the grisly world of Victorian medicine. UK: Penguin Books. ISBN 978-0-14-198338-7. OCLC 1066085821. https://search.worldcat.org/oclc/1066085821

  613. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  614. Gage, Dunbar & Cannada 2023. - Gage M, Dunbar RP, Cannada LK (May 2023). "Open Fractures". Orthoinfo. Rosemont,IL: American Academy of Orthopaedic Surgeons. Archived from the original on 29 July 2024. Retrieved 29 July 2024. https://web.archive.org/web/20240729160246/https://www.orthoinfo.org/en/diseases--conditions/open-fractures/

  615. Godlee 1924, p. 181. - Godlee SR (October 1924). Lord Lister (3rd, Rev. ed.). Oxford: Oxford University Press. ISBN 978-1-333-63431-5. https://wellcomecollection.org/works/j6yczh59/items

  616. Fitzharris 2018, p. 163. - Fitzharris L (2018). The butchering art: Joseph Lister's quest to transform the grisly world of Victorian medicine. UK: Penguin Books. ISBN 978-0-14-198338-7. OCLC 1066085821. https://search.worldcat.org/oclc/1066085821

  617. Fitzharris 2018, p. 163. - Fitzharris L (2018). The butchering art: Joseph Lister's quest to transform the grisly world of Victorian medicine. UK: Penguin Books. ISBN 978-0-14-198338-7. OCLC 1066085821. https://search.worldcat.org/oclc/1066085821

  618. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  619. Gaw 1999, p. 29. - Gaw JL (1999). ""A Time to Heal": The Diffusion of Listerism in Victorian Britain". Transactions of the American Philosophical Society. 89 (1). Philadelphia: American Philosophical Society: iii–173. doi:10.2307/3185883. JSTOR 3185883. https://doi.org/10.2307%2F3185883

  620. Lister 1867b, p. 4. - Lister J (March 1867b). "On a New Method of Treating Compound Fracture, Abscess, etc., with Observations on the Conditions of Suppuration" (PDF). The Lancet. 89 (2272): 326–329. doi:10.1016/S0140-6736(02)51192-2. https://archive.org/download/crossref-pre-1909-scholarly-works/10.1016%252Fs0140-6736%252802%252951077-1.zip/10.1016%252Fs0140-6736%252802%252951192-2.pdf

  621. Gaw 1999, pp. 30. - Gaw JL (1999). ""A Time to Heal": The Diffusion of Listerism in Victorian Britain". Transactions of the American Philosophical Society. 89 (1). Philadelphia: American Philosophical Society: iii–173. doi:10.2307/3185883. JSTOR 3185883. https://doi.org/10.2307%2F3185883

  622. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  623. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  624. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  625. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  626. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  627. Cameron 1949, p. 64. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  628. Fitzharris 2018, p. 189. - Fitzharris L (2018). The butchering art: Joseph Lister's quest to transform the grisly world of Victorian medicine. UK: Penguin Books. ISBN 978-0-14-198338-7. OCLC 1066085821. https://search.worldcat.org/oclc/1066085821

  629. Fisher 1977, p. 137. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  630. Fisher 1977, p. 137. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  631. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  632. Lister & Cameron 1909b, p. 5. - Lister BJ, Cameron HC (1909b). The collected papers of Joseph Baron Lister. Vol. 2. Oxford University Press, Hodder and Stoughton. OCLC 841851608. https://archive.org/details/b31363088_0002

  633. Fisher 1977, p. 136. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  634. Fisher 1977, p. 137. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  635. Fisher 1977, p. 137. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  636. Fisher 1977, p. 137. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  637. Fisher 1977, p. 137. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  638. Cameron 1949, p. 64. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  639. Cameron 1949, p. 49. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  640. Wrench 1913, p. 110. - Wrench GT (1913). Lord Lister; his life and work. London: Fisher Unwin, New York: Frederick A. Stokes Company. OCLC 14798321 – via Cornell University. https://archive.org/details/cu31924012168948/page/n7/mode/2up

  641. Wrench 1913, p. 110. - Wrench GT (1913). Lord Lister; his life and work. London: Fisher Unwin, New York: Frederick A. Stokes Company. OCLC 14798321 – via Cornell University. https://archive.org/details/cu31924012168948/page/n7/mode/2up

  642. Wrench 1913, p. 111. - Wrench GT (1913). Lord Lister; his life and work. London: Fisher Unwin, New York: Frederick A. Stokes Company. OCLC 14798321 – via Cornell University. https://archive.org/details/cu31924012168948/page/n7/mode/2up

  643. Wrench 1913, p. 111. - Wrench GT (1913). Lord Lister; his life and work. London: Fisher Unwin, New York: Frederick A. Stokes Company. OCLC 14798321 – via Cornell University. https://archive.org/details/cu31924012168948/page/n7/mode/2up

  644. Fisher 1977, p. 138. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  645. Fisher 1977, p. 138. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  646. Fisher 1977, p. 138. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  647. Cameron 1949, p. 64. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  648. Kelley 1937, p. 460. - Kelley HA (November 1937). "Reminiscences in the Development of Gynecology". Journal of the Connecticut State Medical Society. 1 (6). The New York Academy of Medicine, Library: Connecticut State Medical Society: 459–467. https://archive.org/details/journalofconnect01unse_0

  649. Listers original letter to his father of 11 June 1866 is printed in full in Cameron 1949.[318]

  650. Fisher 1977, p. 138. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  651. Cameron 1949, p. 64. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  652. Cameron 1949, p. 65. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  653. Cameron 1949, p. 65. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  654. As silk is hydrophobic, the watery solution of carbolic acid wouldn't easily penetrate the material, as any water-based solution would bead when it met the silk. Using the fine Dextrin and starch mixture painted onto the silk allowed the acid to be absorbed into the powder and permeate the material.[320] /wiki/Hydrophobic

  655. Cameron 1949, p. 65. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  656. Cameron 1949, p. 65. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  657. Cameron 1949, p. 65. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  658. Cameron 1949, p. 69. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  659. Fitzharris 2018, p. 168. - Fitzharris L (2018). The butchering art: Joseph Lister's quest to transform the grisly world of Victorian medicine. UK: Penguin Books. ISBN 978-0-14-198338-7. OCLC 1066085821. https://search.worldcat.org/oclc/1066085821

  660. Cameron 1949, p. 69. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

  661. Listers letter to Brougham is published in full in Cameron 1949.[321]

  662. Cameron 1949, p. 69. - Cameron HC (1949). Joseph Lister, the friend of man, by Hector Charles Cameron. London: William Heinemann Medical Books. OCLC 459047072. https://search.worldcat.org/oclc/459047072

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  672. Lister 1867a. - Lister J (21 September 1867a). "On the Antiseptic Principle in the Practice of Surgery". BMJ. 2 (351): 246–248. doi:10.1136/bmj.2.351.246. JSTOR 25212827. PMC 2310614. PMID 20744875. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2310614

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  705. Lister 1867a. - Lister J (21 September 1867a). "On the Antiseptic Principle in the Practice of Surgery". BMJ. 2 (351): 246–248. doi:10.1136/bmj.2.351.246. JSTOR 25212827. PMC 2310614. PMID 20744875. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2310614

  706. Lawrence & Dixey 1992, p. 166. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  707. Lawrence & Dixey 1992, p. 166. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  708. Lawrence & Dixey 1992, p. 166. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  709. Lawrence & Dixey 1992, p. 166. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  710. Lawrence & Dixey 1992, p. 166. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  711. Lawrence & Dixey 1992, p. 167. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  712. Lawrence & Dixey 1992, p. 166. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  713. Fisher 1977, p. 149. - Fisher RB (1977). Joseph Lister, 1827–1912. New York: Stein and Day. ISBN 978-0-8128-2156-7. OCLC 2595463. https://archive.org/details/josephlister18270000fish/

  714. Emphasis is present in the original

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  716. Lawrence & Dixey 1992, p. 167. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  717. Lawrence & Dixey 1992, p. 167. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  718. Lawrence & Dixey 1992, p. 167. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  719. Lawrence & Dixey 1992, p. 167. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  720. Lawrence & Dixey 1992, p. 167. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

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  722. Lawrence & Dixey 1992, p. 168. - Lawrence C, Dixey R (1992). "Practising on principle: Joseph Lister and the germ theories of disease". In Lawrence C (ed.). Medical Theory, Surgical Practice. Routledge Library Editions: History of Medicie. London: Routledge. pp. 153–215. doi:10.4324/9780429020094. ISBN 978-0-429-02009-4. S2CID 70482526. https://doi.org/10.4324%2F9780429020094

  723. Lister 1867a, p. 45. - Lister J (21 September 1867a). "On the Antiseptic Principle in the Practice of Surgery". BMJ. 2 (351): 246–248. doi:10.1136/bmj.2.351.246. JSTOR 25212827. PMC 2310614. PMID 20744875. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2310614

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