Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999 Germ Theory and Antisepsis

By the middle of the 19th century, pain had been banished from surgical operations, but one grave danger still faced every patient submitting himself to the surgeon's knife. This was the ever-present risk of sepsis (infection). Hospital diseases such as erysipelas, pyemia, septicemia and gangrene, were rife. In the 1850s the death rate after amputations varied from 25%-60% in different countries and in military practice it reached the appalling figure of 75%-90%. The first ovariotomies, which were the first abdominal operations performed on a fairly large scale, had a mortality rate of more than 30% even in the most expert hands. That all these diseases were due to some form of "contagion" had long been suspected, but the general view was that whatever agent was responsible was generated spontaneously in wounds. Alternatively, it was theorized that air itself was responsible for suppuration and many attempts were made to exclude the air from wounds by means of elaborate dressings.

Some medical men had postulated the existence of minute particles in the air which carried contagion, the so-called "germ theory." In 1546, Girolamo Fracastoro of Verona (1478-1553) proposed "seminaria, the seeds of disease which multiply rapidly and propagate their life," minute bodies passing unseen from the infector to the infected by contact, by clothing or utensils, and by infection at a distance through the air.

What made the germ theory of contagion so difficult to accept was that no one could see the supposed microbes. Magnifying lenses were used in ancient times, and by the beginning of the 17th century they had been combined in a tube to make the compound microscope. The first man to employ the microscope in investigating the causes of diseases was probably Athanasius Kircher (1601-1680), a learned Jesuit priest. In 1658 Kircher described experiments upon the nature of putrefaction, showing how maggots and other living creatures developed in decaying matter. He also claimed to have found in the blood of plague-stricken patients "countless masses of small worms, invisible to the naked eye." It is impossible that he could have seen the plague bacillus with the very low power microscopes at his disposal, but he may have seen some of the larger microorganisms and his statements about the doctrine of contagion are even more explicit than those of Fracastoro.

The great pioneer of modern microscopy was Anthoni van Leeuwenhoek (1632-1723), a Dutch linen draper, who ground his own lenses and made hundreds of microscopes. Few of his instruments provided a magnification of more than 160X but he is generally credited as making the first observations of germs, reported in his communications to the Royal Society in London. Leeuwenhoek was the first to describe spermatozoa and he gave the first complete account of the red blood corpuscles in 1674; he also found that the film from his own teeth contained "little animals, more numerous than all the people in the Netherlands."

In 1847, Ignaz Philipp Semmelweis (1818-1865), an assistant at the Vienna General Hospital in the maternity clinic (the world's largest at the time), was investigating the 29% postpartum mortality rate among women in Ward One, where births were handled by medical students, vs. a 3% rate in Ward Two where births were handled by midwifery pupils. Semmelweis noticed that the appearances of these deaths from puerperal fever looked the same as those observed in the body of an older colleague, forensic medicine Professor Jakob Kolletschka (1803-1847), who had died from adissection wound suffered in the clinic. He correctly surmised that the postpartum deaths were caused by infection from "putrid particles" carried on the hands of medical students who often shuttled back and forth between the labor wards, the obstetrical clinic, and the autopsy room where dissections were performed. Semmelweis instituted a simple routine of hand-washing with water solutions of chloride of lime, which promptly reduced mortality to 1.27%. Unfortunately, his ideas were met with fierce opposition by the conservative medical community in Vienna, who subjected him to laughter and ridicule. In disgust, Semmelweis left Austria for Budapest. There he became head of the obstetrical division of St. Rochus Hospital, where puerperal fever mortality rates were reduced to below 1% after Semmelweis introduced chlorinated water disinfection.

The man who elucidated the true nature of infection, founded the science of bacteriology, and paved the way for Lister and the antiseptic system in surgery was Louis Pasteur (1822-1895). Pasteur was led to his great discoveries regarding bacteria and other microorganisms by his investigations into the process of fermentation. He showed conclusively that fermentation was brought about by some external agent entering the wine. He proved by painstaking experiments under rigorously controlled conditions that meat and fluids like blood did not putrefy if they were kept in such a way that all air was excluded from them. By taking samples of air at different levels Pasteur showed that contamination became less with increasing altitude. Then he proved that the contaminating agents were living organisms (bacteria) which were everywhere -- in every room, in the air, on every article of clothing, on furniture, on the ground, and on the skin. He showed that putrefaction was caused by the presence of bacteria and that this applied to putrefaction in foods (milk, wine, and meat), urine, and in wounds.

The application of Pasteur's discoveries to surgical practice was the work of Joseph Lister (1827-1912), a young English surgeon who had concluded that it must also be bacteria that caused the suppuration, pus and gangrene which plagued the surgical wards of those days. He determined to prevent the access of organisms by killing them in or on the surface of the wound. Pasteur had shown that heat could kill microbes, but it was impossible to apply heat to a wound without burning the patient, so some chemical substance had to be found. After trying various chemical agents he finally selected carbolic acid, and he insisted that everything which touched the wound, the dressings, the instruments and the fingers, should be treated with this antiseptic. He even produced an antiseptic atmosphere by means of a carbolic spray. The clinical results of Lister's first antiseptic system in 1865 included 11 compound fracture cases with only one death, a 9% mortality rate, marking a watershed between the primitive and modern eras of surgery.

Throughout the 19th century, the arguments continued as to whether microorganisms seen in a sick patient were merely coincidental with the illness, or resulted from the changes brought about by the illness itself. In 1882 the German microbiologist Robert Koch (1843-1910) formulated three famous postulates to guide scientists searching for disease-causing microbes. Koch argued that to prove an organism causes a disease, microbiologists must show that the organism occurs in every case of the disease; that it is never found as a harmless parasite associated with another disease; and that once the organism is isolated from the body and grown in laboratory culture, it can be introduced into a new host and produce the disease again. (An oft-stated fourth postulate, that the microbe must be isolated again from the second host, was not part of Koch's original formulation.2202)* Koch and his pupils discovered specific bacillary causes for various diseases, including anthrax, cholera, tuberculosis, gonorrhea, diphtheria, leprosy, typhoid, trypanosomiasis, and malaria.

* Koch's postulates are still valuable, especially as ideals, but many diseases do not conform to them so they are no longer considered the essential basis of diagnosis that they once were.2202

The theory that specific germs could cause specific disease remained contentious until the beginning of the 20th century. Many scientists of great repute rejected Koch's conclusions, with one scientist confidently asserting that "no microbe found in the living blood of any animal was pathogenic." In one celebrated case, Max von Pettenkofer of Bavaria (1818-1901), a distinguished 19th century experimental hygienist, induced Koch to send him a sample of his cholera vibrios culture and then wrote a letter back to Koch in 1892, as follows:

"Herr Doctor Pettenkofer presents his compliments to Herr Doctor Professor Koch and thanks him for the flask containing the so-called cholera vibrios, which he was kind enough to send. Herr Doctor Pettenkofer has now drunk the entire contents and is happy to be able to inform Herr Doctor Professor Koch that he remains in his usual good health."

Apparently Pettenkofer, aged 74 at the time he wrote the letter, survived this cholera exposure quite well, perhaps possessing the high stomach acidity which sometimes neutralizes the bacillus, though he shot himself to death in Munich 9 years later.

Skeptics notwithstanding, microbes were key. Enormous new vistas now lay open, as surgeons could confidently make an incision through intact skin without incurring an extreme risk of wound infection. The next step was to progress beyond killing wound bacteria with chemical antiseptics, to the prevention of bacterial contamination by eliminating bacteria in the operating theater -- aseptic surgery. The use of steam sterilization of instruments, dressings and gowns, the wearing of masks, caps and gloves, air filtration and the other rituals of the operating theater of today were introduced over the decades following Lister's efforts.

Anesthesia and antisepsis enabled surgeons to carry out procedures that had formerly been quite beyond them, including long operations inside the head, the abdomen and the pelvis. Theodor Billroth of Vienna (1829-1894) resected the esophagus in 1872, parts of the intestines in 1878, and the pyloric end of the stomach in 1881. Billroth also made the first complete excision of the larynx. The first successful repair of a gunshot wound on a major artery was performed in Chicago by John B. Murphy (1857-1916) in 1897; Ludwig Rehn (1849-1930) of Frankfurt am Main performed the first successful repair of a cardiac injury in Germany in the same year.

Writing in 1874, Sir John Eric Erichsen (1818-1896), Professor of Surgery at University College, London, had predicted that "the abdomen, the chest, and the brain would be forever shut from the intrusions of the wise and humane surgeon." By the time of Erichsen's death 22 years later, surgeons had successfully removed from patients the stomach and large parts of the intestines, a whole lung had been excised, and a brain tumor had been extirpated. These operations were not mere feats of surgical showmanship; they saved the lives and restored the health of thousands of human beings.


Last updated on 5 February 2003