Koch Jenner Pasteur Koch Pasteur Pasteur Ehrlich Fleming Domagk 1796 1864 1875 1881-82 1885 1911 1928-9 1935 1941 Ehrlich Fleming Domagk Florey & Chain

Edward Jenner Previous attempts to prevent disease: Inoculation Lady Mary Montagu learned of inoculation against smallpox when she was in Turkey with her husband. In 1718 she introduced the idea to England. A cut was made in the patient’s arm and a thread soaked in pus from the sores of someone with a mild form of smallpox was drawn through the cut. The patient became ill but soon got better. This became popular but some people died During the 1700s Smallpox had replaced the Plague as the killer disease. Victims suffered from a high fever and sores full of pus appeared all over their body. If the heart, brain and lungs became infected then death was certain. Edward Jenner was a country doctor and studied under a famous surgeon called John Hunter, who taught him to learn from scientific observation and experiment. Jenner realised that milkmaids who had caught cowpox (from milking cows) never caught smallpox. In 1796, he carried out an experiment on a small boy to prove his theory correct. He gave the boy cowpox and then, when he had recovered, he gave the boy smallpox. The boy survived. He called this process vaccination because vacca means cow in Latin. Jenner had no idea how his vaccination worked. Many people were against it because they worried that they might turn into a cow. Many people had become rich by offering inoculations and feared they would lose money. In 1802 the government gave Jenner money in order to develop vaccination. In 1840 vaccination was made free for all infants and in 1853 it was made compulsory. Vaccination did not always work and Jenner was criticised for this.

Louis Pasteur Previously… Louis Pasteur was a scientist who first linked germs to disease he proved that germs cause disease – this was called Germ Theory. He made the discovery whilst investigating why alcohol kept souring for the brewing industry. In 1864, he used a swan neck flask to prove that germs in the air caused souring. When his discovery was announced and he demonstrated it in public, many scientists and doctors refused to believe it. Others saw that Pasteur had a definite link between germs and disease/decay. In 1865 Pasteur investigated the silk industry that was in trouble due to silkworms becoming diseased. He was able to prove once again that germs cause disease. He was highly respected for having saved the French beer, wine and silk industries. Previously… Microbes were first discovered in 1677 with the first microscopes. By 1800 most scientists and doctors knew that micro-organisms called germs or microbes existed, but many of them thought germs were a result of disease, not the cause of it. This idea was called Spontaneous Generation Theory (microbes appear by magic when something rots). Some people believed that disease was caused by gases/bad air called miasmas, others believed different theories, but none of them thought germs were the cause. In 1699 a scientist called Francesco Redi boiled a liquid and sealed it against air. No microbes appeared and he decided that infection came from outside. Needham repeated his experiment in 1748 and found microbes. He had used dirty equipment. Some people believed in specificity – that microbes were not all the same and certain ones caused specific disease. A scientist called Bassi linked a specific microbe to the cause of silkworm disease in 1835 and A professor of anatomy called Henle suggested microbes cause infection in 1840 but his ideas were ignored. Anti-contagionists like Nightingale and Farr believed that infections interacted with the environment and caused disease. Their solution was to clean up. Alternatively, contagionists like Simon believed infection was spread by contact with an infected person. Their solution was quarantine or preventing contact.

Robert Koch Robert Koch was a doctor who proved that particular germs cause particular disease in 1875. Koch made his discovery through the use of the microscope, as well as using industrial dyes to stain microbes in order to make them visible. Koch also created a way to grow germs and use his daughter’s pet mice to experiment on. Soon he had a fluid that contained only one germ. He then injected mice with the fluid and they got the disease Septicaemia. Koch proved his work by photographing the whole process with a new lens on his microscope. He also developed a sterile and solid culture to grow germs in, it was called ajar jelly. In 1882 he discovered the germ causing tuberculosis (TB) and in 1883 he identified the germ that causes cholera. He had now identified a germ causing disease in humans Fact… Louis Pasteur was French and Robert Koch was German. Both worked in the late 1800s. In 1870, a war broke out between Germany and France called the Franco-Prussian War. The two men did not like one another

Louis Pasteur Pasteur read of Koch’s achievements with proving that specific germs cause specific disease. He was determined to make more discoveries and win glory for France, which had lost land to Germany after the Franco-Prussian war. Pasteur began working on the anthrax germ (sheep kept dying of anthrax and he was asked to investigate based on his success of helping the silk industry etc). In 1880, he was asked to turn his attention to chicken cholera, as the disease was costing French farming lots of money. Pasteur grew the chicken cholera germ (using Koch’s technique) and told his assistant to inject some chickens to see if they got sick. The assistant forgot to do it and left the germ uncovered for many days. When he realised, the assistant injected the chickens, but they didn’t get sick. He told Pasteur. Pasteur told him to inject them with fresh chicken cholera. The chickens didn’t get sick. He realised that the chicken cholera germ had become weakened when it was exposed to air and had given the chicken immunity. He proved it by repeating the process and also given non-immune chickens cholera at the same time. Chickens that were not given the weakened germ first died. Pasteur realised that germs could be weakened by exposing them to air and then injecting them would give immunity. This was called inoculation/attenuation, but Pasteur called it vaccination in honour of Jenner. In 1881, he repeated the process for sheep anthrax and demonstrated it publically. He had now created a way to prevent animal diseases – chicken cholera and sheep anthrax In 1885 he created a vaccine for rabies and had to try it on a human in order to save the life of a boy (after Koch had shown how to identify germs causing disease in humans in 1882 with TB). He had only been experimenting on animals before this. He was now able to prevent disease in humans. Fact… Louis Pasteur was French and Robert Koch was German. Both worked in the late 1800s. In 1870, a war broke out between Germany and France called the Franco-Prussian War. The two men did not like one another

Paul Ehrlich Paul Ehrlich joined Koch’s research team in 1889 and began working on a vaccine for diphtheria. He became fascinated by the fact that the body naturally produces antibodies to ward off specific germs, without damaging the rest of the body. He called the antibodies “magic bullets” because, like a bullet from a gun, they seek and hit only their chosen target. He wanted to create a synthetic “magic bullet” using chemical dyes. In 1906 the germ that caused Syphilis was identified. Syphilis was a huge problem in the late 1800s and early 1900s – it killed thousands of people each year. His team tried to create a magic bullet to kill the syphilis germ. His team made and tested over 600 “magic bullets” using arsenic compounds. A Japanese bacteriologist joined the team and retested some of the arsenic compounds. He discovered that the arsenic compound Salvarsan 606 did in fact kill the syphilis germ. He tested the compound many times in order to make sure that it always targeted the syphilis germ without harming the rest of the body. Salvarsan 606 was first used on a human patient in 1911. Not everyone welcomes Salvarsan 606 and a cure for syphilis. Doctors said it was painful to inject and some patients died because it was not injected properly. Some doctors thought that it might encourage more people to have more sex, with more people because they now knew that the disease could be cured. Some French doctors refused to use it because Ehrlich was German. Others did not like the idea of putting any form of arsenic into their patients. Fact… Syphilis is a sexually transmitted disease that gets worse the longer it remains untreated. At first, sores developed around the genitals, then the glands swell, then a rash develops on the body, growths appear, patients experience flu like symptoms – tired, headaches and joint pain. Patients experience weight loss and hair loss. Eventually, patients can suffer strokes, dementia, loss of co-ordination, paralysis, blindness, deafness and heart disease. Many victims lost their noses due to tissue being attacked – they caved in. At this stage, syphilis can be dangerous enough to cause death. It can passed to partners and babies in the womb

Gerhard Domagk Gerhard Domagk was inspired by Ehrlich’s work. He set about researching dyes that might destroy microbes which infect the body. Ehrlich had used a separate dye and cure – the dye identified the germ in the body and the Salvarsan then killed it; Domagk wanted to combine the process and find a dye that was a cure. He found a cure for sleeping sickness and then in 1932 he discovered a red dye called Prontosil that could kill the germ causing blood-poisoning. In 1935, he was forced to test it on his own daughter when she got blood-poisoning. He gave her a huge dose of Prontosil; her skin turned red but she recovered rapidly. French scientists discovered that the compound that killed the blood-poisoning germ was called Sulphonamide, which comes from coal tar. Soon, other sulphonamide drugs were developed that could fights diseases such as tonsillitis and scarlet fever. Sulphonamide drugs did have some disadvantages such as they could damage the kidneys and liver and they could not kill very strong germs. Fact… Gerhard was a German bacteriologist and pathologist who was awarded the 1939 Nobel Prize for Physiology or Medicine for his discovery (announced in 1932) of the antibacterial effects of Prontosil, the first of the sulphonamide drugs.

Alexander Fleming Fact… Alexander Fleming was a doctor and medical researcher. Penicillin is not something that can be invented. It is a natural substance. For example, when cheese or fruit goes bad, mould grows on it. This mould has a Latin name, “penicillium”, and has become more commonly known as penicillin. During the First World War, Fleming worked in a military hospital in France. He was appalled that antiseptics such as carbolic acid did not prevent infection in deep wounds. He became determined to find a substance that could kill germs effectively. He returned to work at St Mary’s hospital and in 1922 discovered that a natural substance in tears called lysozyme would kill some germs, but not those that cause disease and infection. In 1928, Fleming was carrying out research into staphylococci, the germs that turn wounds septic. This involved growing the germs on agar jelly, in culture dishes. When Fleming came to clean a pile of discarded culture dishes, he noticed that a mould spore had lodged itself on one of them. He was quick to notice that the germs had stopped growing around the mould. Fleming was curious and did not through it away, like someone else might have done. The mould was a member of the penicillium family and it produced a bacteria-killing juice which Fleming called penicillium. Fleming grew more of the mould and found that it stopped other deadly germs from growing, including anthrax and diphtheria bacilli. He injected it into animals and it didn’t hurt them. However, he would need to turn it into a pure drug in order to use it on humans. Fleming and his colleagues were unable to do this. No-one would give them the specialist help or money that they needed in order to carry out further experiments. Fleming wrote up his findings and published articles in The British Journal of Experimental Pathology in 1929 and 1931. He did nothing more about his discovery. Fact… A man called Sanderson is the first person known to have discovered Penicillium in 1870. He realised that fluid covered in mould, did not produce bacteria. Joseph Lister, who discovered antiseptic surgery, used penicillium in 1871 to treat a cut on the hand of a nurse. He didn’t write anything down or continue his studies of penicillium

Howard Florey and Ernst Chain In 1935 Howard Florey and Ernst Chain began working together in order to carry out medical research. In 1938, Florey’s team decided to study germ killing substances. Chain came across Fleming’s articles on penicillin and set out to produce pure penicillin from the mould juice. They managed to make small quantities of pure penicillin in powder form and decided to test this on animals. On 25 May 1940 eight mice were injected with streptococci. Four were then given regular doses of penicillin and they survived. The other four mice all died within 16 hours. Florey claimed that they had witnessed a miracle. Florey’s team did not have the resources to manufacture large amounts of pure penicillin. They grew the mould in milk bottles, bedpans and milk churns and turned it into pure penicillin by a process of freeze drying devised by Chain. In October 1940 they tried penicillin on a human for the first time. Albert Alexander was a policeman who was suffering from blood-poisoning. He began to recover after receiving penicillin, but died when supplies ran out. Mass production of penicillin remained a problem. They needed the backing of a chemical company that had the resources to mass produce, but Britain was fighting the Second World War and could not help them. Florey realised that penicillin would cure deep infections caused by war wounds and ask USA chemical forms to invest in the mass production of penicillin. At first he was unsuccessful, but in December 1941 the USA entered the war and the US government made grants available for firms wishing to buy equipment o make penicillin. British firms began to mass produce the drug in 1943. In 1945 the Americans estimated that penicillin had saved 1/6 wounded men. After the war the mass production of penicillin became cheaper and more efficient. Fact… In August 1942 a friend of Alexander Fleming lay dying in St Mary’s hospital, London. Fleming contacted Florey and asked for some penicillin to treat his friend. Florey immediately said yes and Fleming’s friend recovered. The story appeared in The Times and on 30th August 1942, Almroth Wright wrote a letter to the newspaper saying that Fleming was the person responsible for penicillin. People began to believe that the development of penicillin was entirely due to Fleming. Even though Florey and Chain were awarded the Nobel Prize with Fleming in 1945, their part in the medical breakthrough was played down.