COVID, chlorine and cleansing.  A story about disinfectants and antiseptics

 

 

“I see the disinfectant, where it knocks it out in a minute. One minute,” Trump said. “And is there a way we can do something like that, by injection inside or almost a cleaning?

 

President Trump was speaking in front of a slide from a presentation by William N. Bryan listing lab studies on SARS-COVID-2 that stated: “commonly available disinfectants (Bleach & Isopropyl Alcohol) work to kill the virus.”[i]

No doubt some listeners wondered whether they should try Trump’s suggestion. (DON’T: bleach is both caustic and poisonous).  Others were horrified or entertained. Some people pointed out that city dwellers drink bleach every day in the water piped from their municipal water systems—but only in minuscule amounts.

For me, the President’s comments raised questions such as why he associated curing with cleansing? Where did bleach come from in the first place?  Who developed the concept of “disinfection,” or thought that drinking a disinfectant might cure a disease?  Did anyone ever try it? How was bleach related to the Victorian-era chemicals such as “chloride of lime” and “carbolic acid” used by doctors such as Ignaz Semmelweis and Joseph Lister—men who allegedly began a medical revolution?  Why did nineteenth-century doctors choose these substances in particular? 

I took a dive into the library and surfaced with the brusque and rotund Scottish philosopher, Dr. John Pringle (1702-1783), Fellow, and later President, of the Royal Society. He was pleased to emerge from retirement. He had tried to resume his career in 1781 while he was still alive, but it had not worked out—possibly because George III still held a grudge about his close friendship with Benjamin Franklin.


 

Despite his frequent collaboration with Franklin, Pringle was no revolutionary. In 1746, he had been serving as physician-general to the British army overseas when the Jacobite army landed in Scotland and British troops rushed back to slaughter his rebellious countrymen at the Battle of Culloden. Pringle witnessed the battle but evidently never commented on it. Travelling with the army across Europe, Scotland, and the North of England, he had noticed that acute diseases were not only attacking his men but were also breaking out in the previously healthy towns where the army set up camp. After settling in London, he embarked on a quest to identify the “septic principle” that he believed had spread fatal diseases through entire communities.

Pringle’s theory that acute diseases were due to a “septic principle” was not new in 1752 when his landmark book Observations on the Diseases of the Army first appeared. Indeed, in his preface he wrote that the idea that “corrupt humours” caused disease had been suggested by the ancient Greek author Hippocrates (c. 460- c. 375 B.C.E.), and was mentioned by the second-century Imperial physician Claudius Galen.  However, Pringle was living in the middle of a transformation in medical theory that rested on fundamental shifts in basic sciences such as anatomy, physics, and chemistry. His theory of sepsis bridged the gap between classical humoralism and modern germ theory.  

Hippocrates had believed that health depended on the climate specific to every given place—its special terroir.  Galen had claimed that the body contained just four distinct fluids or “humors,” each uniting two of the four “elements” of earth, water, air, and fire. In a healthy body, these humors were in balance. For millennia, physicians believed that their primary responsibility was to help their patients counteract changes in the climate and preserve their unique humoral balance: their “temperament.”  Sometimes, however, instead of being properly digested and eliminated, humors became unbalanced or stagnated in the body. They might then “putrefy” and cause sickness as the body struggled to eliminate them. Doctors thought this internal putrefaction was the same process as the rot they saw all around them when animals, vegetables, or dead bodies began to give off foul odors and decay. In order to help the body clean out the putrid fluids that were poisoning it, they bled their patients and emptied out the other decaying fluids with vomits and purges.

The first cracks in this tidy system had come when medieval alchemists using Arabic distillation techniques had created mineral acids (such as hydrochloric acid, nitric acid, and sulfuric acid) from inorganic substances. These proved hard to fit into the theory of the four elements. Later, the arrival of typhus, syphilis, and plague bewildered Renaissance doctors:  the behavior of these communicable illnesses resisted models based on climate, diet, and temperament. Many doctors hypothesized that the vapors escaping from underground vents or the fumes emitted by decaying plants and animals might generate epidemics by releasing poisons into the air that corrupted the body’s internal humors. To combat these poisonous emanations, people tried to overcome stenches with fumigations, fires, and explosions; with the sharp odors rising from volatile substances such as vinegar or smelling salts; and with the soothing scents of flowers and perfumes. 

By the late sixteenth century, the four-element theory of matter that underlay Galen’s four humors was under attack. The visionary alchemist known as Paracelsus raged against the idea. His seventeenth-century follower, Joan Baptista van Helmont, argued that illness resulted from an invasion of the body by a hostile life force, not from humoral imbalances.  He asserted that bloodletting depleted the body’s own vitality and that purges irritated and injured the digestive system without removing the real cause of the disease.  In place of Galenic remedies he claimed that poisonous minerals such as antimony and mercury could be chemically manipulated to modify their harmful “impurities” and produce safer ways to destroy the alien pathogen.  He dreamed of producing a substance pure enough to cure disease without harming the body.

By the early eighteenth century, a growing number of doctors attributed several acute diseases to an unknown entity that invaded the body from outside. There were furious debates about just what this pathogen was and whether it could pass from person to person by contagion. In 1720 a London doctor named Benjamin Martin claimed that some diseases were caused by the microscopic “animalcules” that the Dutch merchant Antoni von Leeuwenhoek had described to the Royal Society.

Pringle is often credited with coining the word “antiseptic,” but this is incorrect. An otherwise unknown “Mr. Place” wrote of “Antisepticks,” in 1721 in a pamphlet on the Plague. He recommended remedies such as cedar, Irish oak, cinnamon, and spices because they both preserved materials against putrefaction and prevented the generation of insects.  Moreover, he wrote, the substances used for embalming in ancient times clearly had resisted rot and insects in dead bodies for centuries, so they might also preserve living ones. 

Dr. John Starr of Liskard sent a letter to Cromwell Mortimer of the Royal Society dated January 10, 1749 describing an epidemic of Diphtheria (“Morbus Strangulatorius’).  Finding a child close to death, he had painted the boy’s throat with a mixture “actuated” with spirit of sea salt (hydrochloric acid) and prescribed “an astringent, detergent, antiseptic Gargle.”  This paper was read to the Society on May 24, 1750 and appeared in Volume 46 (1749-50) of the Philosophical Transactions just a few pages before the first installment of Pringle’s report on his experiments on putrefaction.  Pringle may not have been aware that Starr used the word “antiseptic,” but clearly, he did not invent the word.

The quacks were close behind: on June 9, 1757, W. Steers of Hoxton advertised his “Compound Solution of Myrrh,” for a vast array of ailments, claiming that: “This excellent Solution by its detersive and antiseptic Qualities cleanses the Glands, corrects the Lymph, and purifies the Blood.” This miracle cure for ailments including scurvy, gout, rheumatism, pregnancy, venereal disease, and malaria was apparently distributed as far away as Newcastle and was advertised for more than twenty years.

Doctors are conservative.  Even though the word itself was not new, at mid-century many dismissed Pringle’s “septic principle.” He was determined to show that it caused putrefaction and could be retarded or prevented. After leaving the Army in 1748 he embarked on a long series of smelly experiments. He allowed the serum from human blood to putrefy and showed that it was not, as many believed, strongly alkaline. He found that both ammonia (an alkali) and vinegar (an acid) worked better than salt to prevent putrefaction but they became less effective when they were mixed. He discovered that both strong acids and strong alkalis retarded the corruption of meats, eggs, and blood. Using as his standard the time it took a phial of meat in warm salt water to begin to stink, he developed a table showing the “comparative power of [different] salts in resisting putrefaction.” Then he tried adding other common remedies including cinchona, camphor, myrrh, “Virginia snakeroot” (Aristolocha serpentaria), chamomile, valerian, and many other medicinal herbs to pieces of meat submerged in warm water to see if they slowed the onset of a noxious smell. He also tested dry rubs of cinchona, snakeroot, and chamomile (he does not tell us whether he used Roman Chamomile, Chamaemelum nobile or German chamomile, Matricaria recutita). Although he did not try any of these “antiseptics” on patients, Pringle believed that many popular medicines might slow the decay of the humors in the body just as they did in his phials.

Historian Sydney Selwyn singled out another experiment in which Pringle divided the yolk of a newly laid egg into two equal portions and added equal amounts of water. He then took a thread dipped into the yolk of a putrid egg and added a small piece of the thread to one of his solutions which then putrefied more quickly that the one that was left alone. Thus, Pringle had used a control to demonstrate that the transmission of a material substance caused putrefaction. More than a century later, Joseph Lister would carry out similar experiments with blood, wine and milk using a more precise and refined technique to demonstrate the unique role of living organisms in putrefaction. I have not been able to find any references to Pringle’s work in Lister’s own papers even though it had been famous, if controversial in Pringle’s own day. It won the Copley Medal of the Royal Society in 1750 and appeared as an “Appendix” in numerous editions of his Observations on Diseases of the Army.

Soon after Pringle published his Observations in 1752, a Scottish physician named Edward Wright sent a letter to the Royal Society.  Wright, who would become a Fellow himself in 1759, was hoping to settle a debate about spontaneous generation by looking at infusions of millipedes and beetles through a microscope. He found that the “earlier or later appearance of microscopical animalcules is always in proportion to the degree . . .  of putrefaction” in the surrounding medium. Substances that were considered “antiseptics” such as alcohol and alkaline salts prevented their growth. Referring to Pringle’s experiments, Wright suggested that since the proliferation of these animalcules predicted the “first motion of putrefaction,” viewing them through a microscope could help identify antiseptics.

In 1757, the famous Swedish botanist Carolus Linnaeus claimed that many contagious diseases were caused by different microscopic organisms. Some survived only in bodies whereas others could remain viable in the environment. This explained why some diseases could only spread by contagion when others were widespread in particular locations.  He noted that common disease remedies such as saffron, sulfur, and mercury were also insecticides—implying that their efficacy stemmed from their ability to destroy microbes. In 1764, Pringle added a sort of “stop the presses” note to an edition of his Observations, quoting this passage from Linnaeus’s work and saying that this theory deserved further research.

By the time Pringle died in 1782, many doctors had come to agree that “putrefaction” often entered the body from outside to cause disease and that a wide array of substances could retard its appearance  in a phial (in vitro). The problem was that “antiseptics” that worked in vitro proved to be ineffective in living bodies (in vivo). Others were corrosive or toxic although that did not keep doctors from giving them a try.  

Among the “mineral acids” that Pringle had tested was “spirit of sea salt,” also known as muriatic acid and (later) as hydrochloric acid. In 1756, to combat a “dangerous malignant contagious fever,” a Kidderminster physician who had read Pringle’s work fumigated sickrooms with muriatic acid by adding sulfuric acid to warm salt. Residents in this community continued this practice for the next several decades, as his son indignantly pointed out when a different physician, James Carmichael Smyth, received an award for his work on (allegedly) less-irritating fumigations with nitrous acid.

 In 1773, the Swedish apothecary-chemist Carl-Wilhelm Scheele had dripped some muriatic acid on an ore of manganese and produced a substance later identified as a new element, “chlorine.” In 1795, the apothecary to the military hospital in Woolwich, William Cruickshank, provided directions for generating chlorine gas by mixing salt, manganese, and water, and then adding sulfuric acid. The hospital superintendent believed it cleansed the air contaminated by patients with contagious diseases.

                These fumigations masked or eradicated the fetor that doctors associated with putrefaction, but they were hard to apply and control. English doctors always energetically scoured and washed everything and everyone in sight whenever any acute disease broke out; this relentless cleanliness probably accounts for the success they attributed to their gases. In any case, faith in fumigations soon faded. In the middle of the great cholera epidemic of 1832, the English Board of Health surveyed physicians in the London hospitals who agreed that chlorine gas destroyed unpleasant smells but was useless in preventing contagion. In reviewing the Board’s report, the Lancet confidently if shortsightedly declared that the “mischievous source of delusion” had been fully refuted and “we trust we shall hear no more of the disinfecting agency of chlorine, the chlorides, &c.“  

In 1820, an ambitious French chemist, Antoine Germain Labarraque, had set out to win a prize offered by the French Society to Encourage National Industry. The society was seeking a way to reduce the terrible stench that came from “boyaudiers,” businesses that specialized in cleaning, soaking, and preparing animal intestines. Apart from the sheer unpleasantness of the smell, members of the society feared that the “deleterious gases” were sickening the workers. During a two-year period, Labarraque tried an assortment of chemicals including two preparations with chlorine that were used to bleach fabrics: calcium hypochlorite and sodium hypochlorite (“eau de Javel”). He found that the calcium hypochlorite (chloride of lime) was more effective in reducing the “putridity” emitted by the works but sodium hypochlorite, which had been created in 1788 by the chemist Berthollet, was more suitable for this particular process.  After winning the prize in 1822, he was called in for a more sensitive task: masking the horrible stench coming from the gangrenous body of King Louis XVIII, which was so bad that no one could bear to go near it. He accomplished this by wrapping the king in a sheet drenched with “Labarraque’s solution,” a combination of chlorine with a solution of sodium carbonite.

Chlorine solutions remained popular in British medicine for cleansing and disinfection.  In 1845, the Viennese obstetrician Ignaz Semmelweis was looking for a substance that would destroy the “decaying matter that is generated in diseased patients.” Doctors washed their hands with soap and water after conducting post-mortems, but the smell of putrefaction remained on their hands.  Semmelweis believed that this stench showed that their hands still retained the cadaveric “animal-organic matter,” and needed further cleansing.  After conferring with the cleaning staff, he chose chloride of lime because of its reputation for eliminating bad odors, using one part of chlorinated lime in twenty-four parts of water. He asserted that he did not believe that puerperal fever was contagious, in contrast to the English physicians and noted that:

The English, proceeding from the opinion that childbed fever is contagious, will not visit a healthy maternity patient if they have earlier visited one who is ill unless they first wash with chlorine and change their clothing.  If the number of diseased patients increases, they travel or give up their practice for a time. In those cases where ill patients do not generate decaying matter, English physicians take superfluous steps.

 

Many popular writers have overrated Semmelweis’s originality; as he himself notes, English doctors had been using chlorine solutions for a long time to halt the transmission of puerperal infection.

In addition to the mineral acids that he had tested, Pringle had also tried an assortment of traditional plant-based remedies. Many of these contained phenol, an antioxidant with a long history. Phenolic compounds are found in olive oil and in the essential oil of many common herbs and medicinal plants such as cinnamon and thyme. In the form of pitch, turpentine, bitumen, or tar, either found in nature or obtained from cooking wood, phenolic compounds were applied in classical times to treat wounds and used by the Egyptians to embalm the dead. Eventually through an error in translation, bitumen, which the Arabs called “mūmiyā” became confused with Egyptian mummies, and dead bodies were ground up for medicine. Powdered “mumia” (mummy) lingered in some European pharmacopoeias until the twentieth century.

After the French surgeon Ambroise Paré mixed turpentine with rose oil and egg yolk and used it to clean gunshot wounds in 1537, surgeons employed tree-based phenols as external dressings or ointments, not as internal remedies.  In 1801, a Yorkshire practitioner wrote that he and his family had been using bandages dipped in an ointment containing turpentine and tar “since time immemorial” to dress fractures where the bone pierced through the skin.  However, the Irish bishop and philosopher George Berkeley caused a sensation when he recommended drinking “tar water” made with pine as a cure-all in 1744. 

About 1830 a German chemist, Karl Ludwig Reichenbach, was investigating the tar extracted from beech trees and produced a dark sticky oil. Following Pringle’s example, he tried soaking a piece of meat in the oil.  After he removed it, let it dry, and examined it eight days later, he found that the meat had not putrefied. Soon afterwards, he identified the same oily substance in coal tar.  He named it “creosote” and used it on wood structures as a preservative. A country practitioner tried it as a medicine. According to historian Charles Ambrose, it quickly became a popular remedy.    

In 1834, German chemist Friedlieb Ferdinand Runge discovered a phenol, now known as carbolic acid, in coal tar.  After a prolonged dispute, chemists finally determined that Runge’s acid was just one ingredient in Reichenbach‘s creosote which contains a mixture of antiseptic organic compounds. By mid-century, surgeons were using this carbolic acid instead of the earlier tars and pitches to heal wounds and contusions. Some doctors believed it destroyed the “germs” that Louis Pasteur was investigating; others believed that the powerful smell showed it was attacking putrid vapors or miasma in the air.

                In 1867, the English surgeon Joseph Lister reported that he had successfully used both carbolic acid and a carbolic spray in operations and claimed he had come up with the idea after reading about the way the city of Carlisle had deodorized its sewage in 1864.  Ambrose has concluded that Lister’s actual source was probably his friend Dr. Thomas Anderson, Regius Professor of Chemistry at the University of Glasgow, who just happened to be an expert on sewage.  Anderson, who provided the “crystallized” carbonic acid that Lister used, may also have been Lister’s source for information about Pasteur’s theory of airborne germs.

                Lister’s article provoked a scathing response from James Young Simpson pointing out that Lister had failed to acknowledge the very thorough work of Charles Lemaire and Ferdinand LeBeuf published in 1863. LeBeuf had created carbolic soap (“saponified coal tar”) and Lemaire asserted that it destroyed the microbes that caused both putrefaction and wound infection. Although Lemaire’s work quickly lost its popularity in France, LeBeuf’s carbolic soap is still used around the world for washing hands and cleansing. Ironically, Lister grew worried about the toxicity of his carbolic applications and investigated penicillin as a substitute in 1871 using his own urine as a culture medium. He commented that if a suitable case appeared, he would try it to see if it inhibited the growth of organisms “in human tissues.” He did try it clinically but never published his results.

Chlorine bleach has had a more equivocal history than the plant-based antiseptics.  Trump’s idea that drinking bleach might kill pathogens in the body is not new.  In 1829 a letter signed “Taynton and Williams” reported that the partners had successfully treated scarlet fever patients with chlorine water and “it proved successful in almost every case.”  They were, however, using a weak solution: one drachm of chlorine (1/8 oz) in half a pint of distilled water (10 oz).  Lister’s success with external antiseptics spurred a renewed interest in internal antisepsis.  A Mr. W. G. Balfour wrote to the Edinburgh Medical Journal in 1871 that he had assisted a Dr. Matthew Gardner of Crieff who had given chlorine to children with diphtheria. Balfour thought that it was absorbed into the blood and counteracted the “toxemia” in diphtheria patients. Other physicians tried frequent gargles with chlorinated water or chlorinated steam.  When diphtheria antitoxin was introduced at the end of the century, clinical studies compared it to “chlorine.” However, many of these patients were treated with calcium chloride, a relatively safe salt, not with chlorine. It was probably ineffective but harmless; in any case the diphtheria antitoxin quickly took its place.

            In 1915, Henry Drysdale Dakin, in conjunction with Alexis Carel developed a buffered chlorine version of Labarraque’s solution to cleanse and disinfect wounds.  Like carbolic soap, Dakin’s solution (in a slightly different form) is still in use. It kills bacteria in a wound without damaging the surrounding tissues.  However for most purposes it was superseded by advent of sulfa drugs (derived from chemicals in coal tar) and then by penicillin and other antibiotics.

 Chlorine continues to be a staple of the chemical industry in bleaching, disinfection, and water treatment. Sadly, it has also been used in chemical warfare.  However, its career as a medicine ended at the beginning of the twentieth century.  Roberts Bartholow’s popular textbook stated in 1904 that, “it is irrespirable in sufficient quantity to affect disease-germs in the living subject. . . . Chlorine-water was formerly much employed in scarlet fever, typhoid, typhus, etc.  Its use in these affections was predicated on its power to arrest the growths and development of the morbid ferments.  It need hardly be stated that such notions are no longer entertained.”

If people feel the need for an antiquated antiseptic, they might take a fresh look at Pringle’s experiments.  He found that chamomile was extremely effective at retarding putrefaction. Modern in vitro experiments have revealed that it has antibacterial and antiviral properties, together with a long list of other possible effects.  At least, if chamomile tea fails to cure the problem it will be soothing: something many of us including Mr. Trump might find helpful.

 

 

References

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© Margaret DeLacy

margaretdelacy@comcast.net

July 27, 2020

 


 

[i] Andrew Freedman and Jason Samenow, “Results are preliminary, with many uncertainties remaining President Trump during a White House press briefing Thursday touted recent studies indicating that heat and sunlight can slow the spread of the novel corona virus,”
 Washington Post, April 23, 2020, online article
https://www.washingtonpost.com/weather/2020/04/23/lab-study-coronavirus-summer-weather/