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Antibiotics: the rise and fall of a ‘wonder drug’

By Claire J Roberts, on 12 December 2013

AntibioticsProfessor Peter Taylor (UCL School of Pharmacy) began his Lunch Hour Lecture with a chesty cough – an ironic note to the problems faced by both his immune system and society, as he notes you can’t, of course, cure a common cold with antibiotics. The confusion about this is just one of the reasons for the emergence of dangerous resistance to antibiotics – the subject of Professor Taylor’s Lecture.

He first presented the incontestable fact that antibiotics have changed the world. They are arguably the most important medical breakthrough of the 20th century, with the 1941 introduction of penicillin hailed as a ‘miracle cure’ for infections that could devastate populations (not least because of its serendipitous discovery by Alexander Fleming).

Our 70-year run of antibiotic use is a drop in the ocean compared to the 10,000 years that humans have faced – and succumbed – to these infections.

It was at the point when man began to keep animals as livestock that infectious diseases came to the fore, causing such illnesses as the Black Death, streptococci infections and Typhus epidemics.

Napoleon’s army infamously suffered from typhus after being bitten by lice. They then staggered home, taking their infection with them, and about two million people eventually died from the disease.

The introduction of a drug that could fight these illnesses within just a few days changed modern medicine, allowing organ transplantation, safe surgery, pre-term baby care, chemotherapy… the list goes on.

Along with improved sanitation and immunisation, antibiotics have been a major factor in life expectancy rising from 49, a century ago, to 79 today.

But these “wonderful drugs”, as Professor Taylor affectionately calls them, come with challenges. Now, 70 years after the introduction of antibiotics, there is a huge problem with bacteria becoming resistant to them due to their misuse, overuse and abuse.

Antibiotics are different to normal drugs in that they have an effect on the patient, but also on the microbes themselves – if dosing is not optimal and does not kill all of the microbes, some can develop resistance, and be passed on from patient to patient.

Diagram showing 'natural selection' of resistant antibiotics

This extreme example of Darwinian natural selection is shown in the diagram to the right.

There may be the tiniest amount of resistant bacteria in a person’s system, but if the non-resistant bacteria are killed by antibiotics then only the resistant remain, and multiply, and spread.

This problem is exacerbated by misunderstanding about antibiotics – they are often demanded by a patient for viral infections, which they can’t affect – and the amount of antibiotics in our ecosystem. For example, more than half of the antibiotics we use are pumped into animals to make them fit for human consumption.

Modern ‘superbugs’ – MRSA, TB, C. diff etc. – are lethal examples of this. MRSA has developed resistance to countless antibiotics and it’s only a matter of time before it enters the bounds of the untreatable.

One of the major problems here is that the pharmaceutical industry just isn’t interested in making new antibiotics, which could delay or improve these outcomes. Between 1983–1987 there were 16 introduced, but between 2008–2012, there were just two.

Drug companies are merging, so there is less competition for new discoveries, and antibiotics just aren’t an attractive option for the pharmaceutical industry – they’re expected to be cheap and their use should be limited, so companies risk not returning their investment, which can run into tens of millions of pounds.

Instead, the focus is on high-yield lifestyle drugs – at the moment, there are more anti-obesity drugs in development than antibiotics.

So, what are the alternatives? Is it possible to break the cycle of new antibiotics leading to resistance leading to the need for new antibiotics?

Scientists are currently looking at an infection’s relationship with the immune system to try to answer this.

It’s an unproven but working hypothesis that trying to disable a bacterium, rather than kill it with antibiotics, gives the immune system a better chance of fighting it off itself – potentially without the need for extra drugs. This is called ‘modifying the phenotype’.

One of the ways to wound these nasty cells was actually discovered through a study of green tea.

In one area of Japan, where residents happen to have the highest life expectancy in the world, people were found to drink a huge amount of green tea. Its extracts contain a complex mixture of bioactive molecules, including the antioxidants ‘ECg’ and ‘EGg’.

ECg, in particular, has a fascinating effect on MRSA. While MRSA cells normally multiply easily in a binary fashion, when combined with ECg the cells still replicate but don’t separate well, becoming enlarged, with a rough surface and thicker, lower density walls.

While they didn’t have an effect on the destructive element of the bacteria, these compounds were found to render the MRSA susceptible to other antibiotics, giving the immune system a fighting chance.

It’s at this more optimistic point that Professor Taylor began to describe his own work in disarming pathogens. E-Coli is a famously resistant bacterium, which can travel around the body with the help of a protective capsule.

Without this protective capsule, which can be broken down with a capsule-degrading enzyme, it’s much easier to destroy the cell. A shot of this enzyme, as early as possible after the infection has been identified, can prevent lethal illnesses such as bacterial meningitis.

Professor Taylor leads a team at the UCL School of Pharmacy, which has recently produced an enzyme that can break down the anthrax pathogen’s capsule after just five minutes, allowing for more effective treatment. (This enzyme is thoroughly home-grown – it was originally found in soil taken from Brunswick Square!)

It’s widely acknowledged that returning to a pre-antibiotic age, where all bacteria are resistant, would be disastrous. But Professor Taylor doesn’t subscribe to this pessimistic view, instead offering alternative routes around the problem, and giving the audience that little bit of crucial hope.

For now, the prescription is to drink plenty of green tea, always finish a course of antibiotics and never stop looking at nature itself for solutions.

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