Antibiotics

Bacteria are going to kill you

In Opinion by Morgan Bye3 Comments

The art of medicine consists in amusing the patient while nature cures the disease.Voltaire (1694-1778)

Bacteria ancestors were the first organisms on the planet. Bacteria have survived around 4 billion years on this lump of rock, flying through space. Homo sapiens by comparison have only turned up in the last 100,000 years or so.

Scientists estimate there to be around 5 quintillion bacteria on the planet (that is 5 followed by 30 zeroes)(or 5 nonillion for our US friends). Combined, the weight of bacteria in the world exceeds plants and animals combined.[1]C. Hogan,  Bacteria (2014) – link

As humans have evolved to the complex, multi-cellular and multi-system organisms that we are, we have also evolved a complex defence system against bacteria and other invasive organisms. Yet we still remain weak creatures that can still be decimated by bacteria.

The bubonic plague (Yersinia pestis) of the 16th century was estimated to eliminate a third of the world’s population.

More recently, typhus (Rickettsiae) killed 3 million people, in just 3 years, in Russia alone, as recently as 1918. Typhus even stopped Napoleon from invading Russia.

The cure

Penicillin was famously first observed by Alexander Fleming in 1928.[2]Time Magazine (1999) – link It took a further 13 years before, in 1941, penicillin was first tested experimentally on a human being.

Penicillin went on to hit the mainstream in 1944. Since then we have had 65 glorious years, worry free. Whenever a particular antibiotic was starting to lose effectiveness there was always another to take its place.

Now suddenly, there isn’t.

The Review on Antimicrobial Resistance, on behalf of the UK Prime Minister, projected that antibiotic-resistant bacteria will contribute to 10 million deaths/year by 2050.[3]AMR (2014) – PDF

The truth is, antibiotics simply are not profitable enough. In 2011, the last bastion and long term champion of antibiotics, Pfizer, closed its antibiotic research unit.[4]Chicago Tribune (2013) – link

The other 3 major pharmaceutical companies – Aventis (now Sanofi), Eli Lilly, and Bristol-Myers Squibb — haven’t researched or developed antibiotics since the 1990s.[5]World Health Organisation (2010) – PDF

Given that antibiotic-resistant bacteria are killing 23,000 people/year in US hospitals [6]CDC (2013) – link, President Obama threw $1.2 billion at tackling the antibiotic-resistance crisis — nearly double the amount allocated the year prior.[7]Royal Society of Chemistry (2015) – link

Not that it particularly matters. The Head of the Infectious Diseases Society of America (IDSA), Dennis Maki said[8]Tufts University Newsletter – link

“The development of new antibiotics without having mechanisms to insure their appropriate use is much like supplying your alcoholic patients with a finer brandy.”Dr. Dennis Maki

What happens if we lose antibiotics?

So what happens if we lose antibiotics?

The answer… nothing good.

Immediately we lose care for the serious ill.

The elderly; cancer patients – with weakened immune systems from the chemotherapy or even destroyed immune systems from radiotherapy; organ transplant patients – and the reliance on immunosuppressants to stop the body rejecting foreign organs; to name but a few.

Now consider that so much of modern medicine requires putting something into the body.

…much of modern medicine requires putting something into the body

Take, for example, if you are on regular dialysis often a port is fitted so that large needles do not need to find veins every 3 days or so.

Kidney failure, late stage diabetes, joint replacements and even heart disease – without an ability to insert stents, all become impossible.

Imagine modern medicine with no heart surgery, no neurosurgery, no open cavity abdomen surgery, no C-sections.

Dr. Bhardwaj from Calgary, Canada a regular on Canada’s public radio, CBC, recently stated that:[9]MeanwhileintheFuture (2015) – podcast

… it might be the end of a lot of these miracle cures. Or miracle treatments. Because we can’t do them. We can’t give you a lung transplant because the risk of you getting an infection can’t be controlled anymore. So trying a lung transplant on you is effectively a death sentence if we don’t have effective antibiotics.Dr. Bhardwaj

He goes on to say that even piercings and tattoos become a point of serious risk.

…we know that certain types of piercings have greater risk of infection, so if you know you say, I want a naval piercing, we might say that isn’t viable anymore because we don’t have antibiotics and if you get a naval piercing and then get a skin infection you could die!

In fact, in a world without antibiotics, hurting yourself becomes really dangerous.

In fact, this was known from the first ever patient. In 1941, the first person to ever receive synthesised Oxford penicillin was Albert Alexander, a British policeman.[10]American Chemical Society (1999) – link/PDF He was dying from a staph infection (Staphylococcus), oozing puss everywhere, having already lost his eyes.

The reason he was dying…

He was an avid gardener and he had scratched his face, in the garden, on a rose bush.

He was dying until they gave him penicillin. Overnight Mr. Alexander rallied.

In the end, the staph infection did kill him, but essentially only because they had so little penicillin to treat him with due to wartime restrictions. They were literally taking his urine, filtering out the unmetabolised penicillin and giving it back to him.

In his 1945 Nobel Prize address, Fleming even warned about the dangers of resistance[11]Nobel Prize Archive (1945) – PDF

The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistantSir Alexander Fleming

The future…

So what happens in the future? A future without antibiotics.

Do we give up surgery?

Well no… surgery just becomes different.

In science fiction, all surgery is performed in a bright white, clean room style environment or with some use of a “sterile field”.

Well, the truth is you cannot really do that either

Most surgical or post-surgical infections do not come from the outside world, they come from the bacteria within us…
It is when those bacteria are transplanted from your skin to under your skin, or from your groin to inside your bladder, that’s when they cause problemsDr. Bhardwaj

Surgery then, has to be redesigned.

Redesigned in such a way that contamination of bacteria from one environment is kept to a minimum.

Laparoscopic (key hole) surgery is already a big step in the right direction, originally designed to minimise the amount of recovery a patient must undergo, by minimising the amount of tissue cut apart. Other surgeries will need to be rethought entirely. For example, prostate biopsies currently punch a hole through the rectum and are incredibly prone to infection.

The change is already happening

Medicine is already changing as doctors are holding back antibiotics or sending samples for testing to determine bacterial resistance before choosing an antibiotic.

This is a real shock to doctors, this was stuff that was easy to treat, it was a slam dunk, you give this person antibiotics, they’re good. Now you give them antibiotics and they come back 3 days later and they have a fever and their bladder infection has turned into a kidney infection.Dr. Bhardwaj

In fact, many decisions become interesting.

Typically penicillin is thrown at anyone presenting with strep throat (Streptococcal pharyngitisand it works pretty much universally. Strep throat, in itself, is not dangerous, but there is a remote chance that when your immune system reacts to the infection. It reacts too hard also attacking your heart valves in the process.

In the future, we might not treat strep throat because we want to hold off on the penicillin, and we will take the 1 in 10,000 chance that you’re going to develop heart problems later on to save the antibiotic.

Future recruitment

As antibiotic resistance becomes more prevalent other unforeseeable changes to medicine might occur. When HIV was first outbreaking in the early 1980s, a number of people avoided going into the medical professions, as they did not want to expose themselves, or their families, to that risk.

So what do we do?

The first thing to remember is Douglas Adam’s famous quote, “Don’t panic!”.

Panic is bad, and history has shown that panic leads to an increase in prescribing antibiotics, which only further accelerates the problem.

Medicine is already evolving, doctors are less prone to throwing antibiotics out for every slight cough or throat ache. In many cases, bacteria are tested before antibiotics are before administered.

But what else?

Most importantly, what we need now is to buy ourselves time.

Interestingly, the most promising alternative to antibiotics lies in a long forgotten back-water of science.

British explorers in India, realised that despite the heavy pollution of the River Ganges, the river seemed to have extraordinary healing properties. The British bacteriologist Frederick W. Twort, in 1915, discovered small agents that killed bacteria but did not pursue it further.

The French-Canadian, Félix d’Herelle, went on to discover bacteriophages, often called simply “phages”. Viruses that target bacteria, use them to multiply before exploding – killing the bacteria and spreading the new copies of the virus.

Phage research all-but stopped when penicillin and antibiotics were discovered. Everywhere that is, except behind the Iron Curtain. By the direct orders of Starlin phage therapy continued in the soviet states right up to the end of the Cold War.

One microbiologist from Tbilisi, Georgia recently stated[12]Buzzfeed (2015) – link

At its very peak, when they were supplying the Russian army, the Eliava Institute was producing two to three tons of phages per dayZamphira Alavidze

Whilst the main phage institute has since collapsed, some of the former employees have gone on to cater to medical tourists.

Results, colloquially at least, seem very good. With boasts of US citizen patients being cured of MRSA for a cost of less than $800 compared to a $14,000 antibiotic course.

Of course, there is no promise that moving to phages would prove any better than antibiotics. With time, bacteria could easily evolve again to have protection against phage infection.

In the shorter term, phages present other problems.In the former Soviet block, the health restrictions put on test therapies in no way compare to that imposed by the FDA in the US or the EMA in Europe

Safety remains a high concern. In the former Soviet block, the health restrictions put on test therapies in no way compare to that imposed by the FDA in the US or the EMA in Europe.

Currently, there exists no way of upscaling phage production. Even if it did, as phage technology is over a 100 years old, patents become difficult to obtain. Without patent protection then pharmaceutical companies are unlikely to invest in developing it further.[13]Nature News (2014) – link

Finally, almost all phage therapy requires a personalised cocktail based on the infection and the patient and we have let to mainstream such personalised medicine – the demands on clinical labs would be immense.

About the Author

Morgan Bye

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Morgan Bye is a British science writer, out of Vancouver, Canada, dedicated to helping scientists better communicate their science. He has a Masters in Biochemistry, a PhD in Biophysical Chemistry and even spent time as a scientist at an Israeli research institute.

References   [ + ]

1. C. Hogan,  Bacteria (2014) – link
2. Time Magazine (1999) – link
3. AMR (2014) – PDF
4. Chicago Tribune (2013) – link
5. World Health Organisation (2010) – PDF
6. CDC (2013) – link
7. Royal Society of Chemistry (2015) – link
8. Tufts University Newsletter – link
9. MeanwhileintheFuture (2015) – podcast
10. American Chemical Society (1999) – link/PDF
11. Nobel Prize Archive (1945) – PDF
12. Buzzfeed (2015) – link
13. Nature News (2014) – link