Jack Pacey blogs: From Pasteur to Present – A Brief History of the Treatment of Communicable Diseases

From Pasteur to Present – A Brief History of the Treatment of Communicable Diseases

Over the past 150 years, there have been many developments in almost all areas of science. We have seen a decline in some practices, like astrology and phrenology, and the increase in others, like microbiology. However, possibly the most important development has been made in the field of pathology and bacteriology. In the 19th century, humans lived, on average, for 40 years. Whereas today, that average age has more than doubled in certain places. This is partly due to the increase in general hygiene – a side effect of disease awareness – and the discovery or invention of vaccines. Whatever the culprit may be for causing such a drastic change in life expectancy, we certainly wouldn’t have got here without our knowledge of communicable diseases.

Although this was intended to start at Louis Pasteur it can not go amiss to mention what was believed before his time to show how far we have developed. The initial Germ Theory of Disease (the currently accepted theory that diseases are caused by pathogens) was originally formulated in the mid-1500s; though this had little significance at the time as scientists had no idea how to develop it any further. So, as an alternative ‘humoral pathology’ was the accepted theory. In this, it was believed diseases were a result of an imbalance of one of the four fluids in the body (blood, phlegm, yellow bile and black bile). This hypothesis was originally a Greek theory but was later disproved by many pathologists, including the ‘father of pathology’ Rudolf Virchow who stated ‘Omnis cellula e cellula’ (all cells come from a cell).

Our real knowledge of disease began to truly change in the mid-19th century when Louis Pasteur discovered that fermentation bacteria by a living organism, which he called ‘ferment’; after being asked to look into the science of fermentation by a wine company. Pasteur was able to find out which organisms made up ‘ferment’ through recent microscope developments that took place slightly earlier in the century. Scientists did not know where these organisms came from which inspired Pasteur to boil many different liquids in swan-neck flasks. These experiments lead him to believe that fermentation was caused by microorganisms in the air which were killed when they boiled. This disproved the ‘spontaneous generation theory’ which said that microorganisms that caused fermentation randomly appeared. Late, he developed pasteurization; a technique in which wine is heated to 50-60 degrees Celsius to remove unwanted microorganisms. However, arguably, the most important consequence of Pasteur’s experiments was the identification of certain bacteria and how we could weaken them so that they could be studied or used in vaccinations.

Along with Pasteur, there was Robert Koch who wanted to develop a method for identifying pathogens reliably. Koch started by infecting various healthy mice with the bacteria anthrax. Healthy mice got infected and died whereas mice that acted as controls stayed healthy. This proof that anthrax was the cause of illness along with pasteurisation helped minimise the spread of infectious diseases in the 19th century – partly due to the biology but also due to the awareness that had been raised i.e. the population began to live healthier lifestyles.

After publishing his findings – along with Friedrich Loeffler – on the pathogenic nature of various bacteria (which was of great importance in the microbiology world) he went on to devise a specific method to show whether an organism can be classed as pathogenic or not. This became known as Koch’s postulates: a microorganism or other pathogen must be present in all cases of the disease, the pathogen can be isolated and grown in pure culture, this pathogen must cause the disease when introduced into a healthy animal and the pathogen can be re-isolated and shown to be the same pathogen as the original pathogen. These criteria led to the discovery of over 21 pathogens before the 20th century and were key to the establishment of bacteriology in 1880.

Even though it had been proved that the gods were not the cause of disease and there was a way of identifying pathogens, there was still a discrepancy that even Koch noticed. The postulates could not identify viruses (which had not been discovered at the time); viruses cannot be grown in pure culture. In 1937 Thomas Milton River attempted to cover these problems. He expanded the postulates as follows (for viruses individually): filtrates of infectious material shown not to contain bacterial or other cultivable organisms must produce the disease or filtrates must produce certain antibodies in appropriate animals. Furthermore, even with the addition of these criteria viruses still did not fulfil the other postulates. It is not necessary to show a relationship between the virus and the disease in every case due to the existence of virus carriers (certain animals that carry the virus without being ill). This issue was partly solved later on with the invention of nucleic acid-based methods of microbial identification. Fredricks and Relman adapted Koch’s postulates for the 21st century. When they did this, they mainly based their findings on the DNA found in pathogens. Overall, the creation and development of Koch’s postulates have led to how we identify pathogens today. This has been essential to investigations into how we can improve medication for communicable diseases.

Going back into the late 19th century and just after Pasteur’s discoveries, there was Joseph Lister. He wrongfully assumed that all germs were airborne. Although this incorrect assumption led him, miraculously, to developing a surgically clean treatment. He wanted to create a barrier between the air and the open wound which was being operated upon. He found that carbolic acid was an effective antiseptic as it had already been used in cleaning sewers. Lister’s new method was first used on August 12th, 1865. His results were dramatic as deaths due to surgery dropped from 45% to 15% by 1869 in his Male Accident Ward; mainly due to the reduction of communicable diseases transmitted throughout surgery.

Many advances towards a more surgically clean hospital had already been made in the field of obstetrics (childbirth) before Lister. For example, there was Ignaz Semmelweis who advocated for the disinfection of the hands and clothes of midwives before delivering a child. This led to a decline in cases of puerperal fever. Having seen the decrease in disease in this field, sanitisation and sterilisation made its way into hospitals over the following century. Lister and others marked the start in disease prevention which, other than being incredibly effective, is much more cost-efficient than having to treat each disease individually.

Disease identification is arguably half of the battle. Once we know what a disease is composed of or which disease it is, medicating it becomes immensely easier. Even in the 19th century this was still one of the main aims of biologists. Hans Christian Gram developed the Gram stain which is still used in microbiology today. The Gram stain is used to colour bacteria to make them more visible under a microscope. This played a key part in identifying and, more importantly, classifying bacteria. The gram stain is used to classify bacteria based on certain cell wall properties, they are either gram-positive or gram-negative (with the former turning purple and the latter turning red when a Gram stain is used – a primary stain of crystal violet and a counterstain of safranin). Though this does not allow scientists to classify bacteria down to the species level, it was certainly a move in the right direction.

After Gram, came one of the biggest, if not the biggest, breakthroughs in Pathology since Pasteur: the discovery of the first virus; the tobacco mosaic virus. In 1982, a scientist known as Ivanoski reported that infected leaves remained infected even after filtration through a Chamberland filter-candle (which would have killed off any bacteria). However, it was another scientist – Martinus Beijerinck – who named this new type of pathogen ‘virus’. Although the tobacco mosaic virus can not affect humans (due to the presence of certain antibodies within humans) this still made a massive impact on the world of biology. Leading to certain things like the discovery of more viruses or the development of the aforementioned River’s postulates.

Another big discovery came slightly later in the form of the bacteriophage. Once again furthering the current knowledge of science and how to classify organisms. Ernest Hanbury Hankin was the original discoverer of the bacteriophage although he did not know it at the time. In 1895, he was working in India carrying out studies on the Ganges and the Yamuna river. He noticed that people who drank from some parts of the river could not be infected, or were cured, by cholera (a bacteria). Fredrick Twort was the first to note on bacteriophages in 1915. Having done some experiments of his own he found that when this substance was grown on nutrient agar, some of the bacteria became watery. Although it was not until Felix d’Herelle discovered in 1917 that when added to agar, this unknown agent would cause the bacteria around it to die that they were named. Later coining the word bacteriophage, he tried to apply their use to medicine; this was mostly forgotten due to the introduction of penicillin into hospitals – and was majorly not recognised (in a medical way) again until the 1970s when it was noticed that bacteria could develop immunity to certain antibiotics. Although, very recently Gregory Winter has used phage display technology for the development of human antibody proteins which can be used to treat diseases. The discovery of both these viruses marked large steps in the microbiology world.

1928 was a big year for pathology. It started off with the Griffith experiment that proved that bacteria could transform. This was proved by mixing and adding two different strains of pneumococcus to rats. The lethal III-S strain (smooth) was boiled and the remains mixed with the non-lethal II-R (rough) strain. Together the two managed to kill the rats they were injected into. This showed the transformative properties of bacteria as they merged together. Later came the well-known Alexander Flemming who, by total chance, came across what he named ‘penicillin’ upon observing a mould grow that left an absence of bacteria around it. Although it was not until Howard Florey and Ernest Chain that penicillin found its way into the medical world. They changed it into a drug that is wildly popular and is still one of the most prescribed medical drugs today. However, its popularity has dropped due to the increase in resistance and the fact that it is a mildly common hereditary allergy.
Obviously, one of the main reasons for the drop-in deaths of communicable diseases is vaccines. Whilst Jonas Salk was not the first scientist to invent a vaccine, that dates back to 1796 when Edward Jenner discovered that maids who were or had been infected with cowpox were immune to smallpox, he became an ‘overnight hero’ for developing the vaccine against polio in 1947. At the time polio was one of the leading causes of death and the leading cause of paralysis. At the time scientists did not believe that a dead form of the pathogen could trigger the events of immunisation. Salk proved that this was not the case by experimenting on himself and his family. In 1954 this vaccine was tested on one million children, the Polio pioneers, and was declared effective the following year. Due to how contagious polio was, this was a massive breakthrough not to mention the fact that Salk had proved that it was only necessary for antibodies against the disease to be produced for immunisation to occur.  Salk died in 1995, spending his last few years looking for a vaccine against AIDS. Although this has not been achieved yet, two people have been cured of HIV (at the time of writing) which is so much better than none. But the future for this looks so much brighter, with the use of technology like CRISPR Cas9 which was used in 2015 to cut HIV out of living human and rat cells just to prove it was possible.

Fast-forward to the present we can see the massive changes that have taken place over the last 60 years. Whilst it is almost impossible to mention all the events notable ones include the introduction of the MMR and Hepatitis (A, B and C) vaccines. However recent inventions and discoveries do not seem as impressive unless they are major. This is, possibly, due to the fact we already have the rules we now just need to apply them. Although it could also be due to changes that take place in society; as we become more accepting of individual curiosity, we almost expect people to excel and it does not seem extraordinary. As people begin to listen to what others have to say without immediate dismissal, we too help stop the spread of communicable diseases like in the eighties and nineties when there were massive promotions for condoms to stop the spread of HIV. In the same way that it is much easier and more cost-efficient to create better anti-smoking campaigns than it is to develop better chemotherapies it is easier to lead a healthier life than constantly be visiting a doctor. On the converse, others, arguably, are halting scientific advancements either through not wanting to accept how the world is changing (e.g. from a religious perspective) or through denial of evidence (e.g. the MMR vaccine causing autism). However, overall the role that communicable disease play in the world has diminished greatly and continues to do so; this is down to many of the aforementioned biological developments which have led to not only better medical treatment but also to the fact that more people are aware of what they need to do to remain healthy.

Jack Pacey, Year 13.