1900 – 2000: The 20th century
In 1901, the average life expectancy in the United Kingdom was 47 years. By the year 2000 it had risen to 77 years. New medicines, improved air quality and better public hygiene has contributed to this 64% increase in the life-expectancy. The twentieth century has seen some major advances in healthcare. These have included the development of:
- penicillin: the discovery and development of antibiotics by Fleming, Florey and Chain.
- insulin: Banting and Best’s work to show that insulin can be used to treat diabetes.
- other medicines: pharmaceutical laboratories around the world are constantly producing new treatments for diseases.
Other development
Vaccination: although first described by Edward Jenner in the 18th century, mass vaccination programmes were undertaken to prevent deaths from diseases such as yellow fever, poliomyelitis, measles, mumps and rubella. In 1980 the World Health Organisation announced that the deadly smallpox virus had been completely eradicated.
Medical imaging: physicians can now call on a range of techniques to see inside the body of their patients. X-rays, discovered by Roentgen, were the first but now sophisticated computer technology allows surgeons to plan operations and radiologist to target tumours with pinpoint accuracy. Ultrasound, magnetic resonance imagery (MRI) and computer tomography (CT) scans are all part of the doctor’s diagnostic armoury.
Technology: advances in bioengineering, computing power, materials technology and many other areas of science have led to the development of many medical devices. During heart surgery, an artificial heart and lung machine keep the patient alive. Kidney damage can quickly kill but renal dialysis can keep patients alive even though their kidneys have failed. Hearing aids and cochlea implants bring sound to the hard of hearing. Biotechnology is allowing pure drugs, such as human insulin, to be produced in large quantities.
DNA: the human genome project is unlocking the secrets held within our DNA. It will lead to a much better understanding of the genetic basis for many diseases and may enable the development of new cures in the 21st Century.
The past half century has seen a tremendous advance in medicine. The first heart transplant was performed by Dr. Christian Barnard in 1967 and on July 25th 1978, Louise Brown was the first person to be born after in vitro fertilisation. Research and development of modern medicines has made a massive contribution to the improvement in health and life expectancy.
Two Worlds
Sadly, it is not all good news for medicine in the 20th Century. Many diseases can be controlled and treated but this takes money. In places such as Africa, South America and Asia, the levels of healthcare are below those found in the more well off Western nations. Diseases like HIV/AIDS, cholera, tuberculosis, pneumonia and malaria remain major killers in these regions. The challenge of medicine in the 21st Century is to make high quality healthcare available to all.
Insulin
In 1922, the Canadian physiologists Fred Banting and Charles Best announced to the world that they had discovered Insulin and successfully used it to treat diabetes in a human patient. Until then, diabetics would struggle to grow and there was no successful treatment. They would become walking skeletons and die prematurely due to severe weight loss.
An ancient problem
Diabetes mellitus had been known since ancient times. Egyptian writings from as early as 1500BC described a wasting disease in which the sufferer produced sweet-tasting urine. From the 1850’s onwards, autopsies of people who had died from diabetes suggested that the problem was caused when the pancreas did not function properly. Many physicians speculated that specialised cells, called the islets of Langerhans, produced a chemical that allowed the body to regulate its blood sugar level. Diabetes was caused when this chemical was not produced.
Animal experiments show the solution
Banting and Best worked in the University of Toronto. They removed the pancreas from dogs which then developed diabetes. Their experiments may seem cruel today but without them, insulin would never have been found as the treatment for diabetes.
New methods of testing blood sugar levels allowed Banting and Best to accurately determine the effects of their treatments. They struggled to purify the chemical hormone produced by the pancreas and extracted many compounds from the islets of Langerhans. These were injected into the diabetic dogs to try and find the hormone that would reverse their diabetes.
Initially the injections were very impure and often had fatal side-effects. A team of researchers were recruited and eventually they were able to make an extract from the islets of Langerhans that was pure enough to try on a human patient. In May 1922, fourteen-year-old Leonard Thompson was successfully treated in Toronto Hospital with the extract that they called insulin. In 1928, Oskar Wintersteiner proved that insulin was a protein.
We now know that insulin allows the cells of the body to take in sugar from a digested meal. The liver is especially important in the process of regulating the body’s blood sugar level. Insulin enables the liver to take in sugar (glucose) after a meal and store it as glycogen. This is used later to return glucose to the blood when blood sugar levels begin to fall.
Meeting the demand for insulin
News of Banting and Best’s success spread quickly and soon their laboratory was unable to meet the demand for the new wonder drug.
Commercial preparation of insulin began by extracting it from the pancreas of slaughtered cows and pigs. This is still an important source of insulin for medical use. Chemical modifications tailor the insulin to mimic the human hormone and also give it properties that make it convenient to administer. Early insulins were injected three or four times a day, just before each meal. More long-acting insulins have been developed so that the need to inject so often has been reduced.
Humulin
In 1955 the Nobel Prize-winner Frederick Sanger found the amino acid sequence of human insulin. This allowed a human insulin gene to be made which was then used to genetically engineer bacteria that could produce large amounts of highly pure human insulin. Currently there are 1.4 million people in the UK who successfully control their diabetes by using injections of insulin and much of it is made by genetically-engineered bacteria.
Penicillin
At the start of the 20th century, many people still died from infectious diseases that today are easily cured. It was a discovery by Alexander Flemming in 1928 that would lead to the range of modern antibiotics that we know today.
First Antibiotic
In 1871, Joseph Lister noticed that some moulds could make other microbes grow more weakly. He did not realise the potential of this observation and did not follow it any further. It was over fifty years later, in 1928, that Alexander Fleming made a similar observation.
Fleming was trying to find ways of killing the bacteria that caused cuts and wounds to become infected and turn septic. This was a serious condition and could cause death if the infection spread to the blood. He noticed that the growth of bacteria had been inhibited on a petri dish that had been accidentally contaminated with the mould Penicillium Notatum. He immediately realised that the mould must be producing a chemical that prevented the bacteria from growing. He cultivated the mould and investigated its properties on bacteria that caused diseases such as anthrax, meningitis and diphtheria.
War effort
Fleming’s discovery was not fully exploited until the outbreak of the Second World War in 1939. Infected wounds had caused many deaths in previous wars and two researchers based in Oxford University, Howard Florey and Ernst Chain, were given the task of finding new medicines to treat wounded soldiers. They realised the importance of Fleming’s work and had the resources to grow large amounts of the Penicillium mould. This allowed them to isolate the active antibiotic in sufficient quantities to try it on patients suffering from severe infections.
Before antibiotics, a simple throat infection could easily spread to the lungs and throughout the body. There was little that could be done for these patients and many died from complications of what we would now think of as a trivial infection. Florey and Chain showed that Penicillin could be used to save lives.
The production of Penicillin became a wartime priority and pharmaceutical factories in the USA, United Kingdom and Russia manufactured large quantities of Penicillin which was used to save the lives of wounded soldiers.
Superbugs fight back
There are now many different types of antibiotics which are specialised to treat a wide range of bacterial infections. However, the widespread, and sometimes unnecessary use of antibiotics is leading to the evolution of strains of bacteria that are able to survive all but the most powerful antibiotics. These so-called superbugs can cause real problems, especially in hospitals where patients may become infected after surgery if the highest standards of hygiene are not maintained.
The development of a modern medicine
The industry is constantly developing new medicines. It invests about £8m a day in Research and Development (R&D). This is more than any other manufacturing sector and accounts for about a quarter of the money spent on R&D in the UK.
Discovering new medicines
Teams of chemists, pharmacologists and biologists search for molecules with medicinal properties. Molecular structures are altered to optimise activity and minimise unwanted side effects.
Promising medicines then pass on to the second phase of development. Phase I trials use healthy volunteers to test medicines and gather information on how the body reacts to them. This pharmacokinetic information tells researchers the best way to give the medicine and how it behaves once inside the body. Once this data is available from volunteers, an application can be made to start clinical trials in patients.
At this pre-clinical development phase, additional tests are carried out. These include animal tests to check that the chemical compound is not poisonous and chemical tests to show that it is stable enough to be used as a medicine.
Phase II trials see the new medicine tested in a small number of patients. If it looks to have beneficial effects, the medicine will go on to phase III clinical trials with that include a much larger number of patients to generate significant statistical data.
Placebo
During clinical trials the use of a placebo is vital. The patients are divided into two groups. One group is given the medicine under trial and the other group is given a control medication. This does not contain any of the active ingredients found new medicine and is called the placebo. Neither the patients nor their doctors know if they are using the medicine or the placebo. This acts as a control so that any beneficial effects are due to the medicine and not just because the patient or doctor believe they are using something new and better than their previous treatments.
A massive task
For every new medicine that passes all the trials over 5,000 compounds need to be screened. Each year the UK pharmaceutical industry markets around twenty new medicines. On average It takes an amazing eleven years of development and £500million for each new medicine that reaches the patient.
A technique called high-throughput screening has automated many of the initial tests and pharmaceutical laboratories may now screen thousands of compounds per week. Research chemists can use computers to model designer molecules and using the latest equipment, large pharmaceutical companies may synthesise and screen 300,000 molecules a year.
The development of salbutamol to treat asthma is a typical example of how a medicine is designed tested and produced
Formulating medicine
The formulation of a medicine is how it’s made up. For example, tablets and ointment are both types of formulation. The formulation depends on several factors including:
- how easy it is to take or use
- how quickly a medicine needs to get into the body
- where it has to work in the body
Medawy! 