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As deadly as any bullet

May 14, 2015

Anti-biotic Crisis – the alternative staring us in the face

 

The crisis in effective antibiotics available to us in the future has again hit the headlines today with news that the British government is poised to tackle what is sees as a looming crisis in the longer long term.

To that end economist Jim O’Neill, who had been appointed by Prime Minister David Cameron to head a review, concludes that far more money needs to be pumped into global (and British) drug research if we are to avoid modern surgery, e.g. hip replacements and cancer cures, being a thing of the past.

Future generations will perhaps look aghast at how we threw away our competitive advantage and neutralised our scientific and surgical advancements purely because of our lazy approach to our consumption of antibiotic medications.

The problem is most entrenched in the Third World where medications have to be paid for and where the poor cannot afford to buy a complete course of antibiotics pills so instead they buy only as many as they can afford. Consumption of antibiotics in this way makes them not only less effective for the ailing person but in addition, and as a by-product, then renders their immune system resistant to a course of the same antibiotics pills.

This not only is the infection unable to be checked but unexpected variants of the diseases arise for which the West or advanced countries have no suitable antibiotics. With global travel so universal these days and relatively cheap the prospects of a pandemic are possible with all the ingredients simply awaiting their cue.

To combat this potential the pharmaceutical industry in Britain has been urged to set up a £1.3bn (US $2bn) innovation fund to develop new antibiotics (http://www.bbc.co.uk/news/health-32738332 May 15th 2015).

This blog is usually reserved for military matters and military hardware but on this occasion the medical implications must prevail. Gangerene has always been a problem faced by every Army through the ages and Malaria caused more deaths and pulled more men out of the line than bullets and mortars in the jungles of the Far East. The Ebola panic tell us that other infections are just waiting for their opportunity to flourish. For all the spit-and-polish and shiny new toys every global armed force needs to be well-fed, well-kitted-out, and kept in peak fighting condition.

If the world’s new and old policemen (Russia, China, America and Britain) are to flex their muscles, settle disputes, and defuse hotspots, the deployment of forces must be guaranteed and disease free. So this whole subject is a strategic as well as a tactical matter.

In Sept 2012 I predicted that, “in a few years time there will be no antibiotic available to counter the simplest of infections” (https://motoristmatters.wordpress.com/2012/09/15/34 ), and now this is the view of many others. The Royal Pharmaceutical Society (RPS), in a new report calls for new initiatives to spur companies into discovering new antibiotics, or people will quote start “dying from simple surgery.”

Part of the problems is money. Pharmaceutical firms tend to make drugs that are more profitable, i.e. for long-term conditions, e.g. diabetes, and given that developing a new medicine is a “costly and lengthy process” one can understand that. It can cost up to £1bn to take a drug from an initial idea into the market, in a process that can take 12 years and many other drugs will often fail to reach their true efficacy somewhere along the development process. [1] But overall the cost to any nation of not having effective antibiotics could run in to billions of pounds – not to mention the human misery and devastation affecting every family.

According to Prof Jayne Lawrence (chief scientist at the RPS), the incentives for developing new antibiotics were currently “very poor”, adding that antibiotics were “only used for short periods” and so the volume of sales was lower (than, say, for diabetes sufferers).

The plan

In a series of recommendations, Jim O’Neill says the gap between spending on cancer and antibiotic research needs to be closed. He has estimated that drug-resistant infections will kill an extra 10 million people a year by 2050 and he believes the global cost will spiral to US $100 trillion  (£63tn). [2]

History is not on his side; between 2010 and 2014 the US spent US $26bn on cancer research. In the same period US $14bn went to HIV, yet just US $1.7bn was spent on antimicrobial resistance. The news today is that the British government may be prepared to set aside £1 bn (US$ 1.4bn) as an incentive to the pharmaceutical industry to increase its research activities.

That is all very well but no mention is made of the alternatives to antibiotics, namely, phages. When I wrote my first article on phages in April 2005, none of the health care journals were interested or were simply just ignorant of what phages were and what they could do (and to be fair at the time very little was published in the public domain, see https://motoristmatters.wordpress.com/2012/09/11/33/).

The current plan sees a series of proposed recommendations aimed at tackling resistance. They include:

  • A global “innovation fund” of around $2bn to support new ideas
  • A reappraisal of existing drugs
  • Reduce unnecessary prescriptions through better testing
  • Train a new generation of scientists in the field
  • Track how resistance is spreading

Mr O’Neill said many practices of modern medicine – from chemotherapy to surgery – are only made possible by antibiotics.

  • “I am calling on international funders to allocate money to a fund that can support blue sky science and incubate ideas. Antibiotics research is the poor relation to studying chronic diseases of the developed world but, without antibiotics, treating those diseases can be compromised too.”

Prof Sir John Savill, the chief executive of the UK’s Medical Research Council, voiced his concerns:

  • “Picture a world where a cut finger could kill you, you don’t have to look far – only 100 years ago, a quarter of all deaths were due to bacterial infections. We know there’s no magic bullet to the antimicrobial resistance problem. Real change needs proper global investment. We need to act now.”

Why phages ?

Phages have characteristics not found in antibiotics and tend not to be blunted in their effectiveness even over a long period of time. An excellent reprise of how phages work can be found at “History of Phage Therapy” (http://phages.org/ ). To summarise:-

  • During World War 1 phages were discovered and used to fight bacterial infections. In 1923; the pharmaceutical company Eli Lilly began the commercialization of phage therapy in the US during the 1940s. During the World War 2, phages were used to treat bacterial diseases among Soviet Union soldiers, particularly gangrene and dysentery.
  • Viruses and bacteria evolve over time and can develop a resistance to antibiotics. In theory, this resistance can also apply to phages but it is less difficult to overcome compared to antibiotics because phages are ‘target specific.’ This means as only a one or very few bacterial strains are targeted upon, it is easier to develop new phages than new antibiotics. A time period of only a few days or weeks is needed to acquire new phages for resistant strains of bacteria, whereas it can take years to obtain new antibiotics.
  • Compared to antibiotics, phages go ‘deeper’ into the infected area. Antibiotics have concentration properties but these quickly decrease as they go below the surface of the infection. The replication of phages is concentrated on the infected area where they are needed the most, while antibiotics are metabolised and removed from the body. In addition, secondary resistance does not happen among phages, but happens quite frequently among antibiotic use. Secondary resistance is acquired and occurs when there aren’t enough blood drug levels.
  • Certain infections in people and experimentally infected animals have been proven to be more effectively treated with phage therapy than using antibiotics. Since 1966, the average success rate of studies that used phages in various ways (systematically, topically, intravenously, or orally) is from 80% to 95%, with minimal or no allergic and/or gastrointestinal side effects. The infections studied are from E. coli, Acinetobacter, Psuedomonas, and Staphylococcus aureus. Multiple side effects like allergies, intestinal disorders, and yeast infections have been observed when using antibiotics.

There is, of course, always a down side and this is referred to as “bacteriophage infections” and is found in industries connected to industrial bio-processes such as milk and egg production. Specialist firms have been set up to quickly control and eradicate such bacteriophage invasions/infections in food or other sensitive material.

  • Bacteriophage infections of microbial processes (an unwanted invasion) are relatively common but can be economically devastating. If the designers and operators of bioreactors have an understanding of the biology and ecology of bacteriophages the risks and hazards of bacteriophage infections can be minimised. If an infection should occur it is important to recognize the fact as soon as possible. The symptoms of a phage infection and the procedures for cleaning-up infected bio-process plants are established and well documented.

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REFERENCES:

  1. http://phages.org/
  2. http://www.scientificamerican.com/article/could-bacteria-fighting-viruses-replace-antibiotics/
  3. http://news.bbc.co.uk/1/hi/health/4162119.stm
  4. http://news.bbc.co.uk/1/hi/health/371522.stm

 

 Footnotes:

[1] “Call to discover new antibiotics to stop global crisis” by Pippa Stephens Health reporter, BBC News, 8 May 2014 http://www.bbc.co.uk/news/health-27323474

[2] http://www.bbc.co.uk/news/health-31128971 by James Gallagher Health editor, BBC News website , 5 February 2015

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