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Dr. Manuel Varela: Did Joseph Lister Invent Listerine?

Apr 26, 2017 by

An Interview with Dr. Manuel Varela: Did Joseph Lister Invent Listerine?

Michael F. Shaughnessy –

1) Professor Varela, please excuse my poor attempt at humor, but I would like to ask some questions about Joseph Lister, who lived in the 1890’s and who apparently was known for the use of antiseptic during surgery.  What do we know about this Joseph Lister and his early life?

Dr. Shaughnessy, I am positive that you are not the first one to have made that particular humorous connection between Dr. Joseph Lister and the Listerine mouthwash. Although Lister himself did not develop the chemical agents that constitute Listerine, the mouthwash antiseptic was nonetheless named in his honor by others in 1879.

Lister was the first surgeon known to employ the use of antiseptic chemical agents during surgeries. The honors in his name, however, did not stop with the Listerine. In 1927, the scientific name of a pathogenic bacterium, Bacterium monocytogenes, was renamed as Listerella hepatolytica and then later changed to Listeria monocytogenes, after the then very famous Joseph Lister. The disease caused by this dangerous microbe is referred to as listeriosis. Likewise, an amoeba (a slime mould) was named after Lister, called Listerella paradoxa, and was classified under the scientific family name of Listerelliidae. The technique of using antiseptics during surgery, a method that you referred to in your inquiry, is known as Listerism. Numerous buildings, a hospital, and even an entire institute have been named after him.

The honors did not end with Lister’s name. Lister has been featured in countless biographies, science books, popular films, documentaries, stamps, monuments, and memorial funds.

Joseph Lister was born in a mansion called Upton House on the fifth of April, 1827, in West Ham, a countryside town that resided in a borough of London called Newham, in England. The members of the prosperous Lister family were Quakers, known at the time as the Society of Friends. Lister’s mother, Isabella Harris, has been described by biographers as kind and loving. An early influence on the young Lister was his father, Joseph Jackson Lister, a wine businessman and amateur microscopist who was also a Fellow of the Royal Society and who taught the kid Lister how to use the microscope. In addition to English, the young Lister spoke German and French.

2) Since he seemed to be involved with surgery, I assume or presume that he had some kind of medical training. Where did he go to school and did he have a specialty of study?

While attending Grove House, a Quaker school in a town north of London, called Tottenham, Lister took an interest in anatomy and consequently left the school to begin pursuit in the study of medicine to become a surgeon. As Cambridge and Oxford did not accept Quakers, Lister first went to University College in London, where he struggled with a case of smallpox and then suffered a mental breakdown. His breakdown was attributed to a premature reentry to school before being able to make a full recovery from the dreaded smallpox. He did eventually graduate in 1847 with his BA degree in botany. Lister then returned to University College and studied medicine. Here, Lister flourished, taking his bachelor’s degree of medicine (MB) in 1852 while earning academic honors.

Next, Lister was admitted to the Royal College of Surgeons, England and later became an assistant to the then famous James Syme, Prof. of surgery, housed in the Royal Infirmary at the University of Edinburgh, Scotland. The assistant and professor became lifelong friends.  In fact, Lister courted and later married Syme’s daughter, Agnes. In 1860, the Listers moved to Glasgow, where Lister became Regius chair of surgery. They then returned to Edinburgh in 1869 where Lister became professor of surgery.

In 1877, Lister became chair of surgery in King’s College Hospital housed in London.  He retired from this institution in 1882 and died at the age of 84 on February 10, 1912.

3) Now, the key question seems to be- what led him to believe that the use of antiseptics during surgery would save lives ?

Prior to the use of antiseptics during surgeries in 1865 by Lister, the general state of surgery was fraught with staggering mortality rates, but not after first succumbing to terrifying diseases beforehand. Anesthetics, like ether, developed in 1846, had made surgery a painless and, thus, a significantly less rapidly performed medical procedure. Prior to the use of anesthesia, surgical procedures needed to be as quick as humanely possible, in order to minimize the pain to the patient.

With anesthesia, surgeons could now take their time, carefully probing deeper into living tissues of the patient. Sterile surgical technique had not yet been implemented. Although surgery had now became painless with the anesthesia, more often than not, the patients still succumbed to post-operative infections.

In fact, prior to Lister, post-op infection was actually a completely expected part of the normal consequence of having undergone surgery; a post-op infection was routine. The best case scenario might be a relatively mild, limited infection that would need only pus drainage (referred to a laudable pus), leaving, perhaps, a grotesque scar. The so-called laudable pus was considered a positive sign, nonetheless, that the post-surgical patient might actually live.

The most common scenario, however, was certainly not the best one as described above with the laudable pus. On the contrary, it was death, but often not before first acquiring a more severe post-op infectious disease, like the erysipelas (severe skin rash), the pyremia (high fever—a very bad sign), the putrid gas gangrene (a foul-smelling condition indicating an amputation was soon to be at hand), and the dreaded and putrid sepsis (a blood infection, the same kind that had confounded Semmelweis and countless mothers giving birth).

Treatments of post-op infections were often frightening and, unfortunately, not effective. They included amputations of limbs with dead tissue, pouring boiling oil onto open wounds, and cauterization of infected wounds with red-hot irons. The patient would still acquire the infection and then die. This was essentially the medical state of affair for surgeons during Lister’s time, and he agonized about it for years.

Surgeons of the time had their own idea to explain the post-operative infection and its deadly state of affairs. Because of the miasma (foul-smelling air that was thought to cause disease), the oxygen in the air was believed to play a central role.  Open wounds, like those made in surgery or those made by violent trauma, were obviously exposed to the air. If such was the case, then post-op infections and the deaths associated with them, were simply considered to be unavoidable outcomes.

Lister had a few nagging reservations, however, about the Miasma oxygen exposure theory of post-surgical infections. First, Lister wondered why oxygen that’s presumably embedded deep within tissues didn’t always become infected. According to the oxygen theory, it should have also been infected; it was not.

Second, Lister wondered why lungs that had been perforated by broken ribs didn’t always cause infection in surrounding tissues. According to the oxygen theory, exposure of nearby internal tissue to lung oxygen should cause spontaneous infections there, too. It didn’t.

Third, Lister made the astute observation that for bone fracture injuries in which the skin was broken and bone was exposed, infections arose; while those bone fracture injuries in which skin was intact and bone was not exposed, i.e., so-called closed bone fractures, no infections arose. Thus, Lister reasoned that open wounds, with exposed bone fractures, may have experienced the entry of some foreign agent, other than the oxygen.

Next, Lister tied together the foreign agent wound entry idea with another idea formulated by the great Prof. Louis Pasteur, which held that microbes called bacteria were the germs that caused disease of wine during wine fermentation. Lister reasoned that bacteria were the foreign agents entering the open wounds and causing infections and death.

What Lister did next to the microbes in the surgical wounds was to result in the changing of medical history forever. He set out to kill these wound entering microbes.

Lister sampled infected wounds and using the microscope, he demonstrated that they were indeed teeming with bacteria. Understanding that heat was not practical for treating the infected wounds, he tried a series of chemicals applied directly to the surgical openings. None reduced the infections. He then tried a chemical called carbolic acid. Lister’s choice of carbolic acid came about from reading a report about how its use in the regional sewer system reduced the foul smell of putrefaction.

First, Lister observed that in culture the carbolic acid killed the wound bacteria. Next, although the details are sketchy, in March of 1865, the very first application of the carbolic acid to a patient did not go well, and the patient apparently died. The first successful carbolic acid application, however, did not occur until August 12, 1865. Lister prepared wound dressings that were made of gauze, soaked them with the carbolic acid, applied them directly to a freshly bone-fractured and open leg wound of another patient, and covered the antiseptic-laden dressed wound with tin foil, to prevent the antiseptic from evaporating. The patient was 11-year old James Greenlee, who had been run over by a horse-drawn wagon just hours before Lister’s new history-making treatment was applied. Lister changed the carbolic acid soaked gauze dressings periodically.

Amazingly, not only did the young Mr. Greenlee fail to have a wound infection and not need a leg amputation, he also failed to die. After a few weeks he was released from the hospital in a perfectly healthy state. Feeling invigorated, Lister similarly treated 10 additional patients with his life-saving antiseptic, and 9 of these patients lived, demonstrating that the exposed bone fractures could be treated with antiseptics.

Lister focused his efforts next on patients who had abscesses in their wounds. He prepared a putty containing carbolic acid, among other materials, and he applied the carbolic acid-putty mixture to the abscessed wounds and was met with success. The abscessed wounds healed. Lister published these findings in 1867.

Encouraged by these successes, Lister then used his antiseptic on actual surgical patients. He poured the carbolic acid mixed in linseed oil into surgical openings. He even took to handwashing with the carbolic acid prior to surgery; he soaked the surgical instruments with the same antiseptic. He even sprayed his carbolic acid throughout the whole of the surgical theatre.

Lastly, he dressed the post-operative incisions with gauze containing the carbolic acid. The incidence of post-operative infections greatly diminished.

Lister published these latter findings in a series of journal articles between 1867 and 1875. These publications, recorded in history, outline the very first successful application of antiseptics to the practice of surgery.

4) What was the initial reaction to this in the world of medicine?

Unfortunately, the initial reaction to Lister’s surgical antisepsis technique was plagued with its immediate rejection by the English surgeons outside of his home institution at Glasgow. There are several postulated reasons for this rejection; and chief among them was the fact that the carbolic acid was actually caustic and irritated the skin, including that of the surgeons’ hands. Additionally, although the patient had greatly diminished chances of acquiring post-op infections, the surgical incisions, nonetheless, had to heal from the tissue damage caused by the carbolic acid burns.

Furthermore, the mixture of the carbolic acid and the linseed oil prevented a clear field of vision of the surgical openings during surgeries. This made it difficult for the surgeons to see clearly during surgery. Third, the spraying of the carbolic acid throughout the operating room resulted in its pungent and disagreeable odor throughout the surgical facilities.

In addition, due to its volatile nature, the carbolic acid tended to evaporate, requiring more frequent post-operative changes in bandage dressings than before. This, on top of an already complicated and cumbersome procedure for bandage changing, became a rather bothersome practice.

5) How long did it take before this was widely accepted?

Unlike the case with Ignaz Semmelweis, who never in his lifetime received acceptance for his handwashing method, Lister was exceedingly fortunate in that acceptance of his antiseptic technique came sooner rather than later. Lister enjoyed numerous honors, prizes, tributes and dedications. He was well-respected and greatly admired. Even today, periodic tributes are routinely published in scientific circles. Nevertheless, acceptance of Listerism was not immediate.

In 1869, the Listers moved to Edinburgh, where he had to convince his colleagues there of the benefits of his surgical antiseptic technique. Interestingly, shortly after his arrival, Lister had been summoned to the Balmoral Castle to treat Queen Victoria, who had an axillar abscess. He applied the antiseptic technique during her surgery, and she survived, saving the Queen.  Years later, in 1883, she knighted him.

The first inklings of acceptance for the so-called Listerism began with the French and Germans in 1870 during their war with each other; both sides uniformly adopted Lister’s antiseptic practices, in order to reduce battlefield mortalities from infections. After the war, the military surgeons took the successful antiseptic techniques to their homelands and successfully applied them to their civilian patients, as well. The practice quickly spread throughout most of Europe.

Acceptance of Listerism in the U.S. came more slowly, even after Lister, though widely celebrated at the time with honors and accolades throughout Europe, toured the U.S. from coast-to-coast spreading his message.  In the U.S., Lister was met with skepticism. Medical education in the U.S. largely ignored the newly emerging basic medical science disciplines.

The Americans at the time did not have established practices of sterile technique or of experiment-based medical research, and prominent surgeons openly scoffed about Listerism, even in their popular medical textbooks. Some U.S. surgeons claimed to have tried the antiseptic technique, only to have it fail miserably.

It took the assassination of its president, James A. Garfield, for acceptance of Listerism to take hold in the U.S. On July 2, 1881, Garfield in Washington, D.C., was reportedly shot twice by Charles J. Guiteau, grazing his (Garfield’s) shoulder with one shot, but leaving one of the bullets lodged in the president’s back with the other shot.

Garfield’s physician, Dr. Willard Bliss, a long-time friend and non-believer of Listerism, poked around in the bullet wound with apparently dirty hands and instruments, and it is likely that this is the primary reason why Garfield’s bullet wound became severely infected. Sepsis set in quickly but death for Garfield came slowly, a full 80 days after being shot. Autopsy confirmed death by the sepsis, and the unfortunate incident sparked a renewed interest in Listerism.

The final acceptance in the U.S. was complete when a German physician, Dr. William Stewart Halstead, at Johns Hopkins, implemented Lister’s antiseptic technique during surgery, and it eventually became widespread throughout the country.

Finally, acceptance of Lister’s method in England took place only a full 2 years after his move to Kings College, London, in 1877. Debate about Listerism was contentious during this period, and it was not until a scientific conference, called a congress, was held in 1879 at St. Thomas Hospital, where data were presented showing the improvements (i.e., reductions) in morbidity and mortality rates associated with the use of antiseptic methods during surgery.

Since this congress was first held, surgeons have widely adopted the practice of Lister’s surgical antiseptic method. It further led to the adoption of the sterile technique during surgeries in order to prevent microbial wound contamination of surgical patients in the first place, a process called asepsis.

6) What other discoveries did he make or what else was he known for ?

As a student of surgery, Lister published two papers, one dealing with eye tissue and the other in muscle tissue, both studies of which were based on his use of the microscope. Additionally, Lister is known in microbiology circles for developing a technique in 1879 to isolate bacteria in pure cultures based on their fermentation behaviors, although this latter approach was not as straightforward as those of Koch or even Pasteur.

It did, however, lead later microbiologists to refine Lister’s isolation technique to develop the so-called ‘most probable number’ method to estimate the number of individual bacteria contained within a liquid sample. Lister is also known to have developed several surgical techniques, chief among them being the so-called chromic catgut method, in which the degradable catgut was soaked with chromic salts and carbolic acid and then used in surgery. The chromic catgut technique is still in use today.

7) What have I neglected to ask?

I think perhaps one might be curious to consider the nature of the microbe that was thought to be the causative agent of the sepsis in Lister’s time. Sepsis is a condition in which bacteria actively grow in the blood, as opposed to bacteremia, which is merely the presence of bacteria in the blood. The dread sepsis in Lister’s day was primarily attributable to the bacterium called Staphylococcus aureus, a Gram-positive microbe that produces a golden pigment, visible on Petri plates with culture media as bright golden colonies of bacteria.

Variants of this microbe are known as methicillin-resistant S. aureus (MRSA) and are considered serious pathogens today. A number of years ago, our laboratory studied a MRSA clinical isolate and cloned a gene encoding a multidrug efflux pump, which we called LmrS and which confers resistance to several antimicrobial agents. We recently published another paper in which we were able to inhibit the physiological activity of this LmrS multidrug efflux pump using a cumin spice compound called cuminaldehyde. The bacterium actually has about a dozen of these antimicrobial efflux pumps. In fact, S. aureus has a series of other antimicrobial resistance systems, making treatment of infections with this microbe increasingly problematic. Clearly, much work remains to be conducted in order to ultimately control the devious nature of this historical sepsis-causing microbe.

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