Field of Science
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Change of address1 year ago in Variety of Life
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Change of address1 year ago in Catalogue of Organisms
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Earth Day: Pogo and our responsibility1 year ago in Doc Madhattan
Showing posts with label Microbiology. Show all posts
Showing posts with label Microbiology. Show all posts
#MicroTwJC 49 Expanding the Genetic Alphabet
Recently scientists have achieved a feat the like of which has not been seen in billions of years, they have added new letters to the genetic alphabet of a living organism. What did they do? How did they do it ? Is it too good to be true? All these questions, and more await.
#MicroTwJc 46: FtsZ placement in Bacterial cells
An In depth look at how bacteria divide in "FtsZ placement in Nucleoid Free Bacteria"!
Link: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0091984
Statistical Websites:
1-way ANOVA
http://www.danielsoper.com/statcalc3/calc.aspx?id=43
Tukey's Honestly Significant Difference
http://faculty.vassar.edu/lowry/hsd.html
Microbiology Twitter Journal Club Website for more details:
http://microtwjc.wordpress.com/
MicroTwJC 45: When Antibiotic Resistant Compete (A video presentation)
This summary of the latest Microbiology Twitter Journal Club is going to be different in two ways. Firstly, it's late. Secondly, it's a video. I noticed a while ago that my explanations of papers tended to end up longer than the papers themselves, and I decided to experiment. Here are the results
History of Bacteriology: Miasmas and Contagions
Have you ever found yourself walking down a street, and be confronted with a pungent turd blocking your path?
You don't know where it came from, but whether it be a dog or a tramp, you know to avoid it. It's a natural instinct. Toiletry behaviour can be found all over the natural world. Even tree sloths will make the effort to climb down to defecate far away from where they feed. The disgusting odours we associate with putrefying meat, faeces and death are ones we naturally try to avoid, and when that isn't possible we try to cleanse ourselves thoroughly so that we don't have to experience their stench.
If you were to ask me where the Miasma theory came from, I would point not to any one individual, but to that instinct of disgust. It was it's link to this natural response that also made it so difficult for people to dismiss miasmas even when confronted with overwhelming evidence that they didn't exist.
Many peoples across the world developed their own culture of hygiene and cleanliness, which usually involved some form of cleaning ritual and disposal of waste.
Often, these traditions would propose a specific association between bad smells and disgusting objects with disease. Across the world, incense and pungent smelling products tended to be used for treatments. Getting rid of the smell equated to getting rid of the disease.
Hippocrates advised people to stay away from places with "bad air" in many of his writings, and expounded the earliest iteration of the Miasma theory. His work was translated into multiple languages and passed through the ancient world, forming the basis of medical practice for centuries after his death. The concept of "Bad air" being the cause of diseases became well established. But it was not the only theory of disease people used.
In 1546, Girolamo Fracastoro published "De Contagione et Contagiosis Morbis", where he wrote about the "Contagion" theory of disease. He drew together various observations on disease that he had accumulated over his forty year long career as a physician. He proposed that diseases could be caused by the transfer of some imperceptible, yet corrupt matter between the sick and the well. He called this corrupt matter "the seeds of contagion". He proposed that these seeds could spread in three distinct ways. Through direct contact with infected people, through contact with inanimate objects that had been in contact with sick people (he named these "Fomites") and at a distance. He connected these seeds to "putrefaction", in that they could cause it in their hosts, explaining diseases such as gangrene. His explanations generally attempted to reconcile contagion with Hippocratic theories that all diseases were caused by imbalances between four mysterious "humours" found within the body. The types of disease would be determined by which particular humour interacted with specific seeds.
His work sparked off as debate throughout Europe. Whilst the idea of contagion became more widely known, there was much debate over its theoretical causes and his interpretation of the work of Galen and Aristotle and objection over creating a whole new form of life, these seeds, out of thin air. Fracastoro's most fierce critic was one of the first converts to contagion, Giambattista da Monte. The two would continually clash over the differences in their ideas, a hostile relationship that would eventually develop into one of mutual respect. The students who were privy to these lectures came from all over Europe, and when they returned to their home countries, they would bring the theory of contagion with them.
When proponents of "Bad Air" theory heard of the contagion theory, sparks most conspicuously did not fly. There were arguments, but they were no less vicious than the ones going on between the people who accepted contagion as a theory. Contagion theory still accepted that diseases could be caused by "Bad Air", but that the reason for this was that the air was filled with the "seeds of disease". "Bad Air" Theory held that sufferers of disease were primary sources of "Bad air", and people could catch disease from close contact with the sick.
However, the "Bad Air" theory got a boost in the 17th century when the Hippocratic corpus began to be re-evaluated by a number physicians. I've already talked about a gentleman named Thomas Sydenham who was key for bringing the Hippocratic corpus into the English language and kick starting a new era in evidence based medicine. He lived in an era where doctors applied many treatments based on theoretical ideas, such as bloodletting, sweating and forcing patients to vomit in order to "balance the humors". Sydenham however recognised that many of these treatments did more harm than good, and that the only way to truly divine a theory of medicine would be by a patients bedside.
Unfortunately, he did not have access to the fabulous microscopes of Anton Leeuwenhoek (No-one did, Leeuwenhoek was incredibly protective of his work) so he had no way of determining an evidence basis for contagion. In the end, he tended to favour Hippocratic theories of "Bad air" being the cause of disease, as he had no evidence available to prove otherwise.
In a treatise about malaria* written by Giovanni Maria Lancisi called "On the Noxious Effluvium of Marshes"he connected the disease with the noxious smells emanating from marshes and the mosquitoes that live within them. He gave a name to these noxious smells, he was the first to call them "Miasmas".
The Contagion theory and the Miasma theory were no longer seen as compatible by a growing number of physicians.
His writings went global, and were of particular influence in the United States on medical professionals such as Noah Webster and Benjamin Rush. During an outbreak of Yellow Fever in Philadelphia, many suspected that it had arrived from a contaminated consignment of Coffee from a ship with a crew riddled with the disease. However, Benjamin Rush disagreed with this vehemently, suspecting it had come from the marshy miasma's he believed surrounded the city. Even though Rush believed that contagion played a role in these early cases, that belief eventually waned. By 1799 he actively protested against quarantine procedures for sailors entering the city. By 1805 he began writing treatises to dismiss the idea of contagionism.
Maritime Quarantine procedures were a problem the world over, and cut into the business of many growing companies. It was in the interests of these companies to fuel the backlash against Contagionism.
When quarantine procedures** failed to prevent the Liverpool Cholera epidemic, a major blow was struck to the theory. The Cholera Riots demonstrated the true chaos which could follow a disease epidemic, and spurred people to enact new precautions against these outbreaks. These precautions would be based on the theory of Miasma.
Edwin Chadwick was a major supporter of the Miasma theory, and a vehement anti-contagionist. . He was aware that often, Cholera was associated with unsanitary conditions, and he realised that if the Miasma theory was true, then the greatest threat to peoples health was the presence of open sewers within cities. Through his efforts, open sewers were eliminated, and the cleaning of the streets began to be seen as an issue of public health. These massive clean-up efforts were incredibly effective, and would fuel further support for Miasma theory.
As we now know, Miasma's do not exist, at least not in the form that most people believed in at the time. There are solid reason why humans developed an aversion to particular bad smells. Often the sources of these smells would contain harmful diseases. Clearing out sewage from cities helped people because it meant that flies that fed on faeces could not then transfer microbes from those faeces onto food. It removed opportunities for bacteria such as typhoid from spreading through the streets in shit.
Whilst Chadwick's reforms produced results, they still had problems that are a lot more obvious to modern readers. Whilst the sewers were covered, they still discharged into the water supply, which caused regular outbreaks of cholera and typhus within the city.
Nevertheless, the Miasma Theory had risen to prominence by the 1830's, and its supporters would often define themselves as "anti-contagionist".
But the picture, as always, is more complex. Contagionism, whilst under attack, was far from dead.
*The very name "Malaria" refers to the bad air theory, with "Mal" meaning bad and "Aria" referring to the air. Although it didn't necessarily just refer to our modern interpretation of the disease. Many sweating sicknesses similar to what we understand as malaria would be referred to by its name as well.
** No-one knew of the waterborne nature of the disease, and nor was it thought that fomites could have played a role.
References
Curtis V.A. (2007). Dirt, disgust and disease: a natural history of hygiene, Journal of Epidemiology & Community Health, 61 (8) 660-664. DOI: 10.1136/jech.2007.062380
Nutton V. (1990). The Reception of Fracastoro's Theory of Contagion: The Seed That Fell among Thorns?, Osiris, 6 (1) 196. DOI: 10.1086/368701
Ayliffe G.A.J, English M.P. (2003) Hospital Infection: From Miasmas to MRSA, Cambridge University Press. Link
Often, these traditions would propose a specific association between bad smells and disgusting objects with disease. Across the world, incense and pungent smelling products tended to be used for treatments. Getting rid of the smell equated to getting rid of the disease.
Hippocrates advised people to stay away from places with "bad air" in many of his writings, and expounded the earliest iteration of the Miasma theory. His work was translated into multiple languages and passed through the ancient world, forming the basis of medical practice for centuries after his death. The concept of "Bad air" being the cause of diseases became well established. But it was not the only theory of disease people used.
In 1546, Girolamo Fracastoro published "De Contagione et Contagiosis Morbis", where he wrote about the "Contagion" theory of disease. He drew together various observations on disease that he had accumulated over his forty year long career as a physician. He proposed that diseases could be caused by the transfer of some imperceptible, yet corrupt matter between the sick and the well. He called this corrupt matter "the seeds of contagion". He proposed that these seeds could spread in three distinct ways. Through direct contact with infected people, through contact with inanimate objects that had been in contact with sick people (he named these "Fomites") and at a distance. He connected these seeds to "putrefaction", in that they could cause it in their hosts, explaining diseases such as gangrene. His explanations generally attempted to reconcile contagion with Hippocratic theories that all diseases were caused by imbalances between four mysterious "humours" found within the body. The types of disease would be determined by which particular humour interacted with specific seeds.
His work sparked off as debate throughout Europe. Whilst the idea of contagion became more widely known, there was much debate over its theoretical causes and his interpretation of the work of Galen and Aristotle and objection over creating a whole new form of life, these seeds, out of thin air. Fracastoro's most fierce critic was one of the first converts to contagion, Giambattista da Monte. The two would continually clash over the differences in their ideas, a hostile relationship that would eventually develop into one of mutual respect. The students who were privy to these lectures came from all over Europe, and when they returned to their home countries, they would bring the theory of contagion with them.
When proponents of "Bad Air" theory heard of the contagion theory, sparks most conspicuously did not fly. There were arguments, but they were no less vicious than the ones going on between the people who accepted contagion as a theory. Contagion theory still accepted that diseases could be caused by "Bad Air", but that the reason for this was that the air was filled with the "seeds of disease". "Bad Air" Theory held that sufferers of disease were primary sources of "Bad air", and people could catch disease from close contact with the sick.
However, the "Bad Air" theory got a boost in the 17th century when the Hippocratic corpus began to be re-evaluated by a number physicians. I've already talked about a gentleman named Thomas Sydenham who was key for bringing the Hippocratic corpus into the English language and kick starting a new era in evidence based medicine. He lived in an era where doctors applied many treatments based on theoretical ideas, such as bloodletting, sweating and forcing patients to vomit in order to "balance the humors". Sydenham however recognised that many of these treatments did more harm than good, and that the only way to truly divine a theory of medicine would be by a patients bedside.
Unfortunately, he did not have access to the fabulous microscopes of Anton Leeuwenhoek (No-one did, Leeuwenhoek was incredibly protective of his work) so he had no way of determining an evidence basis for contagion. In the end, he tended to favour Hippocratic theories of "Bad air" being the cause of disease, as he had no evidence available to prove otherwise.
In a treatise about malaria* written by Giovanni Maria Lancisi called "On the Noxious Effluvium of Marshes"he connected the disease with the noxious smells emanating from marshes and the mosquitoes that live within them. He gave a name to these noxious smells, he was the first to call them "Miasmas".
The Contagion theory and the Miasma theory were no longer seen as compatible by a growing number of physicians.
His writings went global, and were of particular influence in the United States on medical professionals such as Noah Webster and Benjamin Rush. During an outbreak of Yellow Fever in Philadelphia, many suspected that it had arrived from a contaminated consignment of Coffee from a ship with a crew riddled with the disease. However, Benjamin Rush disagreed with this vehemently, suspecting it had come from the marshy miasma's he believed surrounded the city. Even though Rush believed that contagion played a role in these early cases, that belief eventually waned. By 1799 he actively protested against quarantine procedures for sailors entering the city. By 1805 he began writing treatises to dismiss the idea of contagionism.
Maritime Quarantine procedures were a problem the world over, and cut into the business of many growing companies. It was in the interests of these companies to fuel the backlash against Contagionism.
When quarantine procedures** failed to prevent the Liverpool Cholera epidemic, a major blow was struck to the theory. The Cholera Riots demonstrated the true chaos which could follow a disease epidemic, and spurred people to enact new precautions against these outbreaks. These precautions would be based on the theory of Miasma.
Edwin Chadwick was a major supporter of the Miasma theory, and a vehement anti-contagionist. . He was aware that often, Cholera was associated with unsanitary conditions, and he realised that if the Miasma theory was true, then the greatest threat to peoples health was the presence of open sewers within cities. Through his efforts, open sewers were eliminated, and the cleaning of the streets began to be seen as an issue of public health. These massive clean-up efforts were incredibly effective, and would fuel further support for Miasma theory.
As we now know, Miasma's do not exist, at least not in the form that most people believed in at the time. There are solid reason why humans developed an aversion to particular bad smells. Often the sources of these smells would contain harmful diseases. Clearing out sewage from cities helped people because it meant that flies that fed on faeces could not then transfer microbes from those faeces onto food. It removed opportunities for bacteria such as typhoid from spreading through the streets in shit.
Whilst Chadwick's reforms produced results, they still had problems that are a lot more obvious to modern readers. Whilst the sewers were covered, they still discharged into the water supply, which caused regular outbreaks of cholera and typhus within the city.
Nevertheless, the Miasma Theory had risen to prominence by the 1830's, and its supporters would often define themselves as "anti-contagionist".
But the picture, as always, is more complex. Contagionism, whilst under attack, was far from dead.
*The very name "Malaria" refers to the bad air theory, with "Mal" meaning bad and "Aria" referring to the air. Although it didn't necessarily just refer to our modern interpretation of the disease. Many sweating sicknesses similar to what we understand as malaria would be referred to by its name as well.
** No-one knew of the waterborne nature of the disease, and nor was it thought that fomites could have played a role.
References
Curtis V.A. (2007). Dirt, disgust and disease: a natural history of hygiene, Journal of Epidemiology & Community Health, 61 (8) 660-664. DOI: 10.1136/jech.2007.062380
Nutton V. (1990). The Reception of Fracastoro's Theory of Contagion: The Seed That Fell among Thorns?, Osiris, 6 (1) 196. DOI: 10.1086/368701
Ayliffe G.A.J, English M.P. (2003) Hospital Infection: From Miasmas to MRSA, Cambridge University Press. Link
#MicroTwJC: Dicing Up Virus Genomes Part 3: The Controversy
In this weeks Microbiology Twitter Journal Club we are going to be discussing two papers published a month ago in Science. These papers purport to provide evidence for RNA Silencing as an antiviral mechanism in mammals.
MicroTwJC: Dicing up Viral Genomes Part 2
Good news everybody ! I managed to source a copy of the second paper for this weeks' Microbiology Twitter Journal club, after not an insignificant expenditure of time and energy.
In the last blog post, I went through the basics of how siRNA mediated silencing works, and how it could potentially be used to attack the RNA genomes of viruses. The paper I reviewed for that post focused on what happened when viruses infected embryonic stem cells, and looked at how these cells chopped up the viral genome into siRNA's.
The paper we will be discussing today will extend that work, focussing on a virus we had just been introduced to in the last #microtwjc post. The authors use Nodamura virus in their studies. Nodamura virus has a positive stranded RNA genome. It produces a protein called B2, which protects viral DNA from DICER and the RNA induced silencing complex.
B2 is a viral suppressor of RNA interference.
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The researchers used a variant of the Nodamura virus with a mutation in B2, so that they could see what happens to the virus without B2 there to protect it.
So without further ado, let us get to the first experiment.
History of Bacteriology: The Cholera Riots
Murmurs of murder rippled through the crowd as it accumulated outside the entrance of the building, cursing the people who entered and exited it. They had watched helpless woman stretchered into the building, knowing she would soon join of the hundreds of people who had died within its walls. Whole city of Liverpool was in uproar, and had endured enough.
References
History does not record who threw the first stone, but soon the air was thick with them. They thudded against the buildings wall's, breaking the windows and scattering the people within. The men and women escaping the building were chased and beaten.
The building was Toxteth Park Hospital, the people being chased were Doctors and nurses, and this was the beginning of the Liverpool Cholera Riots.
It was the age of the Industrial Revolution, Empire and Mass migration. Irish immigrants formed a major part of this migration, travelling to America to avoid the depredations back home. The primary intersection between the British Isles and America was a Liverpool. Immigrants awaiting passage to the new world would often find themselves stuck in the overcrowded city of Liverpool.
Like many cities of this era, Liverpool was transforming into a haven of squalor and disease. Urine and faeces were flung freely into the streets where they flowed into the rivers from which people drank. Tuberculosis and Typhoid ravaged the poor.
The industrialization of Europe had meant that transport links had become much quicker, and trade had improved, but brought with it diseases. Rags from continental hospitals sold to farmers in Yorkshire to help manure hops also carried with them a disease that had not been seen in England before. It was known as "Asiatic Cholera" * at the time, and it frightened the rich and poor alike. Before its appearence, "Cholera" had only referred to seasonal stomach bugs and diarrhoea, and didn't relate to the deadly bacterium which we now refer to as Vibrio cholerae.
The month after the infected rags had been imported into Hull, the first cases of Cholera began to be recorded. Patients suffered from diarrhoea, severe cramps, followed by severe dehydration and then death, with the final symptom being the patients turning blue. It could turn a healthy person into a corpse within twenty four hours.
In 1831, an epidemic devastated Sunderland, killing over 20,000 people. The doctors could not contain the outbreak, their treatments consisting of brandy, bleeding and opium. Fear of this disease was high when it reached Liverpool in 1832.
A veteran medic who had experienced Cholera first hand whilst stationed in India tried his best to calm the situation. After the first two cases reported in Liverpool, he publicly stated that this "was not the case of an epidemic" like people may have heard about in Europe or Dublin. Not long after this, Cholera broke out on a vessel named the Brutus, claiming eighty-one deaths. Liverpool's Board of Health were slow to act, at first apparently denying the news of the outbreak within their city. At the boards very outset it was criticised as being filled with "a few fat-bellied magistrates" who had obtained their position through patronage rather than any medical expertise. Their sluggish reaction to this epidemic did not help that public perception.
The hysteria surrounding this disease was only rivalled by the scandal surrounding the whole medical profession. In the early half of this century, medical schools suffered from a dearth of human cadavers for students to practice on, and had begun to pay quite handsomely for them. In Edinburgh, two enterprising gentleman by the names of Burke and Hare decided to capitalise on this need by making a few corpses of their own, killing 16 people and making approximately £8K in today's money. The complicity of the medical establishment in this case combined with widespread reports of grave-robbing and the publics general distaste for dissection stained the medical establishment. People were now well aware of the high prices doctors would pay for a good corpse. A patient walking into a doctors surgery may have worried that they could be worth more dead than alive.
When Cholera began to spread through Liverpool people began to refer to doctors as "Burkers", invoking the more notorious of the murderers and implying that doctors were profiting from the deaths of their patients.
The medical board in the meantime were doing their best to contain the disease, setting up new hospitals for patients to go to, and arranging carts to carry sufferers to these hospitals. The doctors and nurses worked hard to help their patients, but were severely hampered by the fact that none of their treatments appeared to work. In fact, it is likely that treatments like bloodletting made the disease a lot more dangerous.
Things however came to a head when Mr Clarke and his wife fell ill from Cholera. The doctors were jeered at by the mob when they brought the woman into the building. At this point the Liverpool Chronicle picks up the story.
“Stones and brickbats were thrown at the premises, several windows were broken, even in the room where the woman, now in a dying state, was lying, and the medical gentleman who was attending her was obliged to seek safety in flight. Several individuals were pursued and attacked by the mob and some hurt."
The next few days saw the protests escalate. Mobs prevented doctors from carrying away their patients by any means necessary. They would halt the palanquins that were used to carry patients away, and when that didn't work they started to smash them to pieces. In one incident, people opted to hide a patient away from a surgeon tasked with treating her, and upon confronting them is chased across town to take refuge in a shop. Nightly gatherings surrounded the hospital in Toxteth Park. The police were often called in to hold back the worst excesses of the violence, but were simply overwhelmed.
But it wasn't just the fear of the doctors that motivated people. Cholera hospitals were rapidly being set up, bringing sick people to places of business. Some of those in the crowd wanted the doctors to take their grisly business elsewhere. Conspiracy theories abounded about how doctors were perpetuating the epidemic for a £10 "cholera fee" paid out by local bureaucrats. In some cities, Grocers believed doctors were advising people from staying away from certain food, leading them to be pelted with fruit.
The riots in Liverpool were solved when a threatening letter was sent to the mayor of the city. In the content of the letter, the author promised to do "wicked things" to any doctors who attempted to treat their patients. The author signed the letter off simply as "An Irishman". It was this last part of the message that suggested an alternative solution to the violence. Most of the cholera victims were the Irish Catholics crammed together within cramped underbelly of the city, and they were the loudest voices speaking out against doctors.
The Board of Health invited the Catholic clergy into a meeting to discuss solutions to the violence, and the clergy were given a message to deliver to their congregations. The speech addressed people fears about the cholera outbreak, and more importantly announced in no uncertain terms that the people who were dying were not being dissected. Furthermore, they declared that people had the right to go into the hospitals to see this for themselves, and to see the untouched bodies of their deceased before burial.
This was supported by an article published in the Liverpool journal by Dr James Collins , who also made a point of talking to people during church meetings.
Soon, the streets of Liverpool were once again relatively quiet.
These riots occurred before anybody had a real handle on how infectious diseases spread. It was an era where the doctors had little idea of how to control a cholera outbreak, nor even what truly caused it. But the massive death toll and the incredible civil unrest spurred the government into action nonetheless. At this point, people had started to make the connection between overcrowding and poor sewerage to the spread of disease. The government would soon take steps to solving these problems, but in the process promote a troublesome theory that nearly strangled the nascent science of microbiology in its crib.
References
Burrell S. & Gill G. The Liverpool cholera epidemic of 1832 and anatomical dissection--medical mistrust and civil unrest., Journal of the history of medicine and allied sciences, PMID: 16144959
Gill G., Burrell S. & Brown J. Fear and frustration--the Liverpool cholera riots of 1832., Lancet, PMID: 11476860
Howie W.B. (1981). Stephen T. Anning, The history of medicine in Leeds, Leeds, W. S. Maney, 1980, 8vo, pp. ix, 218, illus., [no price stated], (paperback)., Medical History, 25 (04) 442-443. DOI: 10.1017/S002572730003502X
Further Reading
The First Spasmodic Cholera Epidemic in York, 1832, Issues 37-46 By Michael Durey
Howie W.B. (1981). Stephen T. Anning, The history of medicine in Leeds, Leeds, W. S. Maney, 1980, 8vo, pp. ix, 218, illus., [no price stated], (paperback)., Medical History, 25 (04) 442-443. DOI: 10.1017/S002572730003502X
Further Reading
The First Spasmodic Cholera Epidemic in York, 1832, Issues 37-46 By Michael Durey
* The only doctors who had observed it were those who had been serving in the armed forces in the Empire when this disease swept through India during the Kumbh Mela, hence why it is known as Asiatic Cholera. A second pandemic had been working its way across Europe.
History of Bacteriology :The Rebirth of Microscopy
It was Robert Hooke who first popularised microscopy when he published his seminal work in "Micrographia". He had produced exquisite images of the eye of a fly, of tiny fleas, and of the tiny structures within a cork plant, naming them "cells". However, within five years of its publication, many of its findings were overshadowed by the work of a mysterious Dutchman.
The Dutchman in question was a successful garment seller who had developed a keen interest in Microscopy. In his workshop he had quietly begun to develop some of the most advanced microscopes of his era. This man was Anton Leeuwenhoek, and is often credited as the "Father of Microbiology".
He created the first microscope powerful enough to see the Microbes. He could see organisms too small to be visible to the naked eye, and stunned the world with his intricate drawings of these tiny creatures. He was the first person to discover the existence of single celled organisms, and his regard spread throughout Europe.
Robert Hooke became a massive fan of Leeuwenhoek, and a supporter of his work. He had but one problem. The entire field of microscopy was "Reduced to a single Votary, which is Mr Leeuwenhoek". Whilst the world was filling with astronomers, mathematicians and naturalists, there was only one person who was looking into the tiny world of single celled organisms.
Robert Hooke became a massive fan of Leeuwenhoek, and a supporter of his work. He had but one problem. The entire field of microscopy was "Reduced to a single Votary, which is Mr Leeuwenhoek". Whilst the world was filling with astronomers, mathematicians and naturalists, there was only one person who was looking into the tiny world of single celled organisms.
Why was Anton van Leeuwenhoek the only microscopist left in the world ?
Hooke believed that it was the lack "of the inquisitive genius of the present age". i.e. no-one was interested in the subject. But there were somewhat justifiable reasons why people weren't interested in microscopy.
Leeuwenhoek was intensely defensive of his discoveries, fearing that some other may come along to take the credit. It was an understandable fear. Quite notably Robert Hooke had a long standing dispute with Newton over who discovered gravity first, and believed that Newton had purloined his ideas on the inverse square law and gravitational attraction*.
This is why Leeuwenhoek kept his methods secret, apprenticed no students, and refused to show anyone the microscopes he had used to make his discoveries. Leeuwenhoek's place in history was secured, but his legacy was not.
When Leeuwenhoek died, he took microbiology with him. Whilst microscopes could be found in some places, they were merely curiosities with no practical function for those wanting to push the boundaries of science. They were incredibly difficult to use, and often produced distorted images, due in part to chromatic aberration. No-one knew how Leeuwenhoek got around these problems, and it would be a long time before anyone would create microscopes of comparable power.
Solving Chromatic Aberration
Lenses work by re-directing light into a focal point by taking advantage of light slowing down when it enters glass. Using shaped glass allows you to bend light, and focus it to magnify an image.
Lenses work by re-directing light into a focal point by taking advantage of light slowing down when it enters glass. Using shaped glass allows you to bend light, and focus it to magnify an image.
Each part of the wavefront entering the lens is slowed down, but because of the shape of the lens, they are all slowed down for different lengths of time, causing them to be distorted. This means that wavefronts coming out of the convex glass end up focused on one point.
This effect is the basis for telescopes, spectacles and your eye's ability to read the words I've just typed.
Here is the problem. Any optical material can split different wavelengths of light. This is what happens when we pass light through a prism, or when it goes through the raindrops to form a rainbow. The different wavelengths of light are slowed down to different speeds, which is what causes them to separate.
This effect is what causes chromatic aberration.
This effect is what causes chromatic aberration.
Chromatic aberration causes multiple images of different colours to have different focal points. This results in blurry and miscoloured images. Leeuwenhoek's microscopes had sidestepped these problems by being incredibly small, and didn't suffer from chromatic aberrations due to the incredibly small distances involved.
It was an amateur optician named Chester Moores Hall who eventually solved the problem. The answer came to him as a result of his studies of the human eye. He noticed that the human eye itself had a spherical lens, so why wasn't human sight blighted with chromatic aberrations ?
He hypothesised that the jelly like vitreous humour in the eye held the answer. Somehow, the vitreous humour cancelled out the aberrations caused by the lens. He decided to use a similar method to compensate for the chromatic aberrations. He knew that some glasses would separate light in the opposite way to others. So if he used a type of glass that would naturally bend light the opposite way to the lens, he could use it to cancel out the splitting of light caused by chromatic aberration. He decided to use flint glass to form a cover over the lens, and theoretically correct for any aberration.
He had one big problem. He didn't know how to grind his own lenses. He needed to get someone to make his special lenses, but he didn't want any of them to figure out that he had solved chromatic aberration.
To keep his discovery secret, he used different lens-makers to make each part of his new invention separately. One would make the objective lens, and the other would make the corrective cover for it.
But Chester Moores Hall fell victim to an unfortunate coincidence. Neither of these lens makers could make the parts he requested, and both of them decided to subcontract the work onto a man named George Bass. When he constructed both of the primary parts for the lenses, he literally put the pieces together, and figured out what Chester Moores Hall had done.
To keep his discovery secret, he used different lens-makers to make each part of his new invention separately. One would make the objective lens, and the other would make the corrective cover for it.
But Chester Moores Hall fell victim to an unfortunate coincidence. Neither of these lens makers could make the parts he requested, and both of them decided to subcontract the work onto a man named George Bass. When he constructed both of the primary parts for the lenses, he literally put the pieces together, and figured out what Chester Moores Hall had done.
George Bass mentioned this discovery to another optician, John Dollond, who had also been struggling with the same problem. Dollond immediately patented this discovery, and started selling corrective lenses that accounted for chromatic aberration.
It was his son, Peter Dollond, who decided to fully enforce those patents. By this time, many other opticians around London were using chromatically corrected lens. Peter Dollond managed to use his fathers patent to try to run them out of business. In the subsequent legal proceedings, Dollond's competitors believed they had an ace in the hole. They called Chester Moores Hall to the stand, who confirmed that he was indeed the true inventor of the achromatic lens, giving them the right to dispute the patent.
The problem was that Chester Moores Hall kept it to himself, which became a major sticking point for the judge. The Judge ruled in favour of Dollond, because Dollond had tried to make a profit from his invention.
It was a Dutch instrument maker named Jan van Deijl who had managed apply achromatic lenses to microscopes. But he wanted to get them absolutely right, and spent such a long time perfecting them that the work had to be passed down to his son Harmanus, who would eventually publish that work and set up a company to start selling microscopes. They suddenly became popular again, and scientists like Giovanni Amici and Joseph Jackson Lister* made further improvements to this design. Microscopy had been successfully rescuscitated.
Soon these instruments were in high demand, with microscope manufacturers popping up across Europe, and then across America. They became the essential tools for naturalists and physicians, and microscopy became the forefront of important research during this era.
During the next month I will be writing a series of posts on the history of microbiology, focussing mostly on the massive leaps that happened during the 19th century. If I was to point at one reason why microbiology would finally came into its own during this era, I would point you to the microscope. Many of the greatest discoveries of this era simply would not have happened if these instruments had not become fixtures on the desks of reputable scientists around the world, waiting to be used.
During the next month I will be writing a series of posts on the history of microbiology, focussing mostly on the massive leaps that happened during the 19th century. If I was to point at one reason why microbiology would finally came into its own during this era, I would point you to the microscope. Many of the greatest discoveries of this era simply would not have happened if these instruments had not become fixtures on the desks of reputable scientists around the world, waiting to be used.
References and Further Reading
Cassedy J.H. (1976). The Microscope in American Medical Science, 1840-1860, Isis, 67 (1) 76. DOI: 10.1086/351546
Dobell, Clifford (1932). Antony van Leeuwenhoek and His "Little Animals": being some account of the father of protozoology and bacteriology and his multifarious discoveries in these d
Dobell, Clifford (1932). Antony van Leeuwenhoek and His "Little Animals": being some account of the father of protozoology and bacteriology and his multifarious discoveries in these d
isciplines. New York: Harcourt, Brace and Company.
Department of the History of Science (Harvard) Description of Harmanus Van Deijl's compound microscope
Nineteenth-century Scientific Instruments by Gerard L'Estrange Turner
Peter Dollonds answers Jesse Ramsden -http://www.mhs.ox.ac.uk/sphaera/index.htm?issue8/articl5
* The impression I get from what I've read is that Robert Hooke, like many scientists of his era had come up with the rough idea that celestial bodies attract eachother, and that attraction dissipates with distance, but it was Newton who actually went ahead and created a mathematical model with a series of quantifiable laws to explain these phenomena. Hooke had the rough idea of what was going on, Newton had the detailed explanation.
** Not to be confused with his son, Joseph Lister, the pioneer of antisepsis.
#MicroTwJC: TCA Cycle and Voltammetry
This weeks Microbiology Twitter Journal club focuses on the electrifying bacterium known as Shewanella. This species of bacteria has been found in iron and heavy metal rich sediments, and can respire metal as we would respire oxygen. This paper is all about respiration, and looks at one part of how organisms convert chemicals into energy that they can use. For a rough overview, check this out
For organisms like us, who use oxygen as the main electron acceptor, we can simply transport the oxygen to our mitochondria where respiration is occurring. But for bacteria like Shewanella, that use iron as their electron acceptors, they can't transfer iron into their intracellular compartments as easily, so they have moved a significant part of their electron transport chain to their surfaces. So when they metabolise compounds, they charge their surface. The bacterium's ability to reduce metals have lead to some exploring how it can be used to detoxify heavy metals in the environment, and others exploring how it can be used in a microbial fuel cell.
We may lose the most important antibiotics you've never heard about
This is a story about the most important human antibiotic you've never heard of. It is one that has protected us long before Fleming, Domagk and Ehrlich were even born. We may be on the verge of losing it, with disastrous consequences.
In the last century, we beat back the bacteria that plagued us with an arsenal of antibiotics. But the bacteria are clawing their way back, evolving new ways to resist antibiotics. As our best antibiotics are rendered useless against infections, we are forced to look at alternatives to these treatments.
Consider Colistin. This antibiotic was found to be produced by a soil bacterium named Bacillus polymyxa in 1949. Colistin is formed from amino acids and kills bacteria by targeting their surface membranes.
In the years after its discovery, it grew to be used worldwide. But it wasn't to last.
For antibiotics like penicillin, were often advised to increase the dose beyond the levels deemed necessary to kill of most bacteria, so as to prevent resistance developing. For drugs like penicillin, which only have mild side effects, such overdosing rarely produces any side effects for the patient*. So doctors could prescibe it, and other antibiotics like it in high doses without any fear of it harming their patients.
Colistin was a different kind of beast. An overdose of Colistin could lead to severe kidney damage and neurotoxicity. Thus, the natural tendency to use higher doses of antibiotics that strictly necessary backfired severely when applied to Colistin. As a result of these side effects, Colistin fell out of favour in the 1980's.
Fast forward to the present day. A large number of our most commonly used antibiotics no longer work against multi-drug resistant superbugs.
Those safety concerns which caused Colistin being pulled out of circulation in the end worked in its favour. Since it had not been used in such a long time, few bacteria had acquired resistance to it. At the turn of the century it became a key weapon in our antibiotic arsenal, the drug of last resort, to be brought out to fight only the hardiest of superbugs.
However, the situation is always changing, and now bacteria have begun to develop resistance to this drug.
Whilst Colistin resistant bacteria are being found with increasing regularity, the loss of Colistin may not be the most disturbing part of this development. It's the worrisome fact that Colistin resistant bacteria may also be able to fight off the other antibiotic; the antibiotic I alluded to in the introductory paragraph.
It is not just bacteria like Bacillus polymyxa or fungi like Penicillium chrysogenum that can produce antibiotics. We can do it too.
We naturally produce our own antibiotics, which are known as Cationic Antimicrobial Peptides, or CAMPs. You may not have heard about these compounds, but they have protected you and your ancestors since they crawled out of the ocean. They form an integral part of our Immune system, and are manufactured by a number of important immune cells to combat bacteria. These antibiotics are constructed from amino acids, and target bacterial membranes, just like Colistin.
A recent paper in mBio suggests that the similarity of Colistin to human antimicrobial peptides could potentially have dire consequences.
To test whether this was a possibility, scientists decided to test whether bacteria that were resistant to Colistin were also resistant to human antimicrobials.
They looked at Acinetobacter Baumannii, a bacterium that is often linked with hospital acquired infections, and one that is also known to develop Colistin resistance. They found a number of these Colistin resistant strains of Acinetobacter and found that many of them had developed some degree of resistance to human antimicrobials. The bacteria that were vulnerable to Colistin were also still vulnerable to human antimicrobials.
But they went further. They took samples of bacteria from afflicted patients from the initial stages of infection, and from the late stages and observed the development of this kind of resistance in real time.
These results suggest that forcing the evolution of Colistin resistance could also push them to develop resistance to human antimicrobials. Under normal circumstances, the immune system's careful management of our internal bacterial community has prevented this kind of resistance emerging.
This paper suggests that the extensive use of Colistin may force bacteria into a position where resistance to our innate antibiotics can become much easier for them. Not only will they be resistant to our best treatment, they will have the tools to combat a key part of our immune system, and allow them to cause deadlier diseases.
Napier B.A., Burd E.M., Satola S.W., Cagle S.M., Ray S.M., McGann P., Pohl J., Lesho E.P. & Weiss D.S. (2013). Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in Acinetobacter baumannii, mBio, 4 (3) e00021-13-e00021-13. DOI: 10.1128/mBio.00021-13
*unless you are allergic to penicillin, in which case any contact with the drug could be dangerous.
#MicroTwJC: Bacteria in SPAAAAACE !!
In 2011, Stephen Hawking declared that humanity may not survive to see the next millenium "without escaping beyond our fragile planet." That may seem like an overly dramatic statement, but there is some truth to it. As long as we confine ourselves to earth, we tie our fate to the fate of this world. It is a big uncaring universe containing unstoppable threats that can any time blast us from the surface of this world.
If we want to ensure that our species survives, we need to colonise space. This is a challenge that no other life form (as far as we know) has achieved. There are no environments on earth that can possibly prepare us for the fatigues of space. We evolved without having to worry about radiation, within the constant grasp of gravity. If we are to make space our home, we need to figure out how to adapt our physiology to make it hospitable.
The paper being reviewed in this weeks Microbiology Twitter Journal Club aims to investigate how our bacteria will be affected when we go into space. Our gut encompasses an entire bacterial ecosystem that is essential to our health, and that we still barely understand. We know that when bacteria adhere to the surfaces within the body, they aggregate together into convoluted structures known as biofilms. These colonies allow the bacteria to communicate with each other, and survive within the harsh environments of the body. A biofilms are critical to bacterial survival within the body, and by proxy, could be crucial to our survival. But what happens to these films when they are grown in space ?
How do we even find out ?
It's simple. We go there.
Antibiotics & Agriculture part 5: Stokstad's Genie
When Robert Stokstad discovered antibiotic growth promoters, he was operating in industrial farming's nascent era. In the 1920's, farmers realised that with the right levels of vitamin supplements, they could raise chickens indoors safely cocooned from the outside environment. But this innovation came with some costs, as chicks born in this environment had poor survival, and didn't grow as fast as they did in the wild.
Stokstad's discovery of growth promoters was like a wish come true. Just by adding a low dose antibiotics, we could help more chicks survive into adulthood, and allow them to grow to full size whilst saving money feeding them. But, just like in any morality tale, wishes can come with consequences.
It turns out that the wholesale saturation of the industrial farming environment with antibiotics provided the perfect incubator for antibiotic resistance.
There have been a number of dangerous outbreaks of antibiotic resistant pathogens which can be traced directly to their usage in the agricultural industry. Salmonella, E.coli and even some strains of Staphylococcus aureus have acquired resistance to antibiotics from farms.
Even more disturbing is that agricultural antibiotic usage has increased the numbers of resistance genes in the overall environment. These genes have been proven to transfer between different bacterial species. Even if the bacteria they reside in are themselves not a threat to human health, these genes can be transferred to pathogens that are threats.
The mounting evidence of this threat prompted some countries to act.
In 1984, after hearing reports that consumer confidence in meat safety was dropping, due to the antibiotic resistance threat, Swedish farmers requested a ban on all growth promoters. They were the first country to implement a ban, but they were not the last.
If you wanted to show the pitfalls of banning agricultural growth promoters, you can find no better example than that of the Netherlands. In these cases, the ban came into force before the farmers could improve infection control practices. As a result, they were beset by outbreaks of bacterial disease that required the use of more therapeutic antibiotics. In the Netherlands, this meant that there was no net change in the amount of antibiotics sold to the agricultural industry.
Sweden was not immune to this effect. Whilst the initial results of the ban showed promising reductions in antibiotic use, it was also characterised by increases in disease outbreaks on farms. The appetite for therapeutic antibiotics increased in direct response to these outbreaks, until it eventually rose to pre-ban levels.
When Denmark embarked on a similar plan to ban antibiotic growth promoters, they did so with an eye on the experiences of previous nations. With this system, they managed to reduce antibiotic use by around 90%. Somehow their ban managed to reduce infections without changing the welfare of their animals, and still managed to keep the Danish pig industry competitively priced.
So why did the Danish experience differ so much from the experiences of other nations ?
When they implemented the ban, they also ensured there was a comprehensive monitoring system in place to send out the alarm if new antibiotic resistant bacteria were produced, and a way of regulating the doses of therapeutic antibiotics given by veterinarians. They didn't ban all of their growth promoters at once. They first rolled back the use of avoparcin in 1995, then followed it with a ban on virginiamycin in 1998, and then finally a ban on all growth promoters in 2000. This gave the farmers the time to change the way they did farming to compensate for the loss of these growth promoters.
In preparation for the ban, Danish farms implemented basic infection controls. The routine disinfection of workers clothes, the workers themselves and their vehicles is now standard in many countries, to prevent the transfer of diseases between farms. Veterinary vigilance became watch words, with herds regularly inspected to ensure that outbreaks were caught and dealt with as early as possible.
The authorities also madee sure that every part of their system was committed to the reduction of antibiotic use. Veterinarians were prevented from directly selling antibiotics to farmers, they could only issue prescriptions, removing a potential conflict of interest. The numbers of antibiotic prescriptions given to specific herds was carefully monitored. Farms that were consuming high levels antibiotics could be spotted more easily under this system, and given the appropriate support.
Denmark also brought in new laws which changed the way that their pigs were raised and weaned. They recognised that a lot of their infection problems could be traced to their piglets being weaned too early and forced into an infection riddled world without the protective antibodies in their mother's milk, and immune systems not fully able to deal with the infection riddled world into which they were being exposed.
When Denmark put its ban in place, it did so with the knowledge that a massive full spectrum ban on antibiotic growth promoters could potentially harm its precious pork industry. When they drew up plans to ban antibiotic growth promoters, they paid attention to the science. They thought carefully about the consequences of the ban, and how they could best compensate for these effects using the best science available. Then they brought in the ban slowly, allowing farmers and veterinarians time to adapt to the new system, and ensured that the incentives presented by this new system were geared to limiting further usage of antibiotics.
In 2006, a broad ban on all antibiotic growth promoters was implemented across the European Union in response to mounting public pressure. Countries across the EU are now for better or for worse have to adapt their farming strategies to compensate for the loss of antibiotic growth promoters.
There are signs that the ban is working. The numbers of antibiotic resistance genes in the environment are decreasing.
But let's not pop the champagne corks just yet. There are a few problems with these bans that require further inspection.
In the initial stages of all the bans, outbreaks of bacterial disease often occur more frequently. In some scenarios, Veterinarians can be reticent in prescribing more antibiotics to treat these diseases, leaving the animals to suffer longer, and exposing them to greater risk of death. Improvements to infection control and animal husbandry only go so far in preventing outbreaks of disease. The situation in some countries is so bad that banning agricultural antibiotics actually increases the numbers of therapeutic antibiotics being used. The levels of antibiotics in some cases reaches the levels seen before the ban.
Every time an antibiotic is used, be it in animals, or in humans, has a chance of increase the numbers of resistant strains in the population. Taking this viewpoint, you may say that some of these bans have no effect at all. But you would be ignoring a crucial detail.
In his Nobel prize speech, Fleming himself gave a warning about how mass underdosing could trigger the creation of antibiotic resistant strains, yet within ten years underdosing became standard practice within the agricultural industry.
It is crucial that we make sure that antibiotics are always used responsibly. The key reason why banning antibiotic growth promoters was that it was one demonstrable case in which antibiotics were used irresponsibly.
The other key problem with these bans is that no one knows the extent to which it will affect human health. It should prevent new strains of antibiotic resistant bacteria evolving on farms, such as livestock associated MRSA, or antibiotic resistant Enterococci.
However, expecting these bans to eliminate all antibiotic resistance is to unfairly place all of the blame on farming and agriculture for our current situation. The primary environment in which antibiotic resistant bacteria most commonly evolve, and where they are at their most dangerous, is found in hospitals. Any antibiotic resistance genes which have already made the jump into this environment are here to stay. Regulating antibiotic use in hospitals is difficult, because that is where we, as humans, need them the most. As much as we may worry about how the price of meat may be affected, if we cannot accept that relatively minor sacrifice, we will not be able to accept the changes and the costs needed to eradicate antibiotic resistance from our healthcare systems.
The genie of antibiotic resistance is out of the bottle, but it wasn't just Robert Stokstad who had a hand in releasing it. We may sneer at growth promoters because they are the worst example of how we have squandered antibiotics. We may lament at how some faceless evil within the agri-business made the calculation that our future is worth trading for cheaper meat today. But we all had a hand in shaking the genie out of its bottle. We still have a hand in determining our own future. Even those of us who currently live in Europe may soon be inundated with american meat raised antibiotic growth promoters if certain trade agreements are successful. They will once again be faced with the same choice facing everyone else in the world, the choice between a full stomach today or better health tomorrow.
References
The WHO's internal evaluation on the termination of antimicrobial growth promoters in Denmark
http://www.who.int/gfn/en/Expertsreportgrowthpromoterdenmark.pdf
Danish Pig production in a European Context
http://www.lf.dk/~/media/lf/Aktuelt/Publikationer/Svinekod/LFEUBenchUK110318.ashx
Cogliani C., Goossens H. & Greko C. (2011). Restricting Antimicrobial Use in Food Animals: Lessons from Europe, Microbe, 6 (6) 274-279. DOI:
Stokstad's discovery of growth promoters was like a wish come true. Just by adding a low dose antibiotics, we could help more chicks survive into adulthood, and allow them to grow to full size whilst saving money feeding them. But, just like in any morality tale, wishes can come with consequences.
It turns out that the wholesale saturation of the industrial farming environment with antibiotics provided the perfect incubator for antibiotic resistance.
There have been a number of dangerous outbreaks of antibiotic resistant pathogens which can be traced directly to their usage in the agricultural industry. Salmonella, E.coli and even some strains of Staphylococcus aureus have acquired resistance to antibiotics from farms.
Even more disturbing is that agricultural antibiotic usage has increased the numbers of resistance genes in the overall environment. These genes have been proven to transfer between different bacterial species. Even if the bacteria they reside in are themselves not a threat to human health, these genes can be transferred to pathogens that are threats.
The mounting evidence of this threat prompted some countries to act.
In 1984, after hearing reports that consumer confidence in meat safety was dropping, due to the antibiotic resistance threat, Swedish farmers requested a ban on all growth promoters. They were the first country to implement a ban, but they were not the last.
If you wanted to show the pitfalls of banning agricultural growth promoters, you can find no better example than that of the Netherlands. In these cases, the ban came into force before the farmers could improve infection control practices. As a result, they were beset by outbreaks of bacterial disease that required the use of more therapeutic antibiotics. In the Netherlands, this meant that there was no net change in the amount of antibiotics sold to the agricultural industry.
Sweden was not immune to this effect. Whilst the initial results of the ban showed promising reductions in antibiotic use, it was also characterised by increases in disease outbreaks on farms. The appetite for therapeutic antibiotics increased in direct response to these outbreaks, until it eventually rose to pre-ban levels.
When Denmark embarked on a similar plan to ban antibiotic growth promoters, they did so with an eye on the experiences of previous nations. With this system, they managed to reduce antibiotic use by around 90%. Somehow their ban managed to reduce infections without changing the welfare of their animals, and still managed to keep the Danish pig industry competitively priced.
So why did the Danish experience differ so much from the experiences of other nations ?
When they implemented the ban, they also ensured there was a comprehensive monitoring system in place to send out the alarm if new antibiotic resistant bacteria were produced, and a way of regulating the doses of therapeutic antibiotics given by veterinarians. They didn't ban all of their growth promoters at once. They first rolled back the use of avoparcin in 1995, then followed it with a ban on virginiamycin in 1998, and then finally a ban on all growth promoters in 2000. This gave the farmers the time to change the way they did farming to compensate for the loss of these growth promoters.
In preparation for the ban, Danish farms implemented basic infection controls. The routine disinfection of workers clothes, the workers themselves and their vehicles is now standard in many countries, to prevent the transfer of diseases between farms. Veterinary vigilance became watch words, with herds regularly inspected to ensure that outbreaks were caught and dealt with as early as possible.
The authorities also madee sure that every part of their system was committed to the reduction of antibiotic use. Veterinarians were prevented from directly selling antibiotics to farmers, they could only issue prescriptions, removing a potential conflict of interest. The numbers of antibiotic prescriptions given to specific herds was carefully monitored. Farms that were consuming high levels antibiotics could be spotted more easily under this system, and given the appropriate support.
Denmark also brought in new laws which changed the way that their pigs were raised and weaned. They recognised that a lot of their infection problems could be traced to their piglets being weaned too early and forced into an infection riddled world without the protective antibodies in their mother's milk, and immune systems not fully able to deal with the infection riddled world into which they were being exposed.
When Denmark put its ban in place, it did so with the knowledge that a massive full spectrum ban on antibiotic growth promoters could potentially harm its precious pork industry. When they drew up plans to ban antibiotic growth promoters, they paid attention to the science. They thought carefully about the consequences of the ban, and how they could best compensate for these effects using the best science available. Then they brought in the ban slowly, allowing farmers and veterinarians time to adapt to the new system, and ensured that the incentives presented by this new system were geared to limiting further usage of antibiotics.
In 2006, a broad ban on all antibiotic growth promoters was implemented across the European Union in response to mounting public pressure. Countries across the EU are now for better or for worse have to adapt their farming strategies to compensate for the loss of antibiotic growth promoters.
There are signs that the ban is working. The numbers of antibiotic resistance genes in the environment are decreasing.
But let's not pop the champagne corks just yet. There are a few problems with these bans that require further inspection.
In the initial stages of all the bans, outbreaks of bacterial disease often occur more frequently. In some scenarios, Veterinarians can be reticent in prescribing more antibiotics to treat these diseases, leaving the animals to suffer longer, and exposing them to greater risk of death. Improvements to infection control and animal husbandry only go so far in preventing outbreaks of disease. The situation in some countries is so bad that banning agricultural antibiotics actually increases the numbers of therapeutic antibiotics being used. The levels of antibiotics in some cases reaches the levels seen before the ban.
Every time an antibiotic is used, be it in animals, or in humans, has a chance of increase the numbers of resistant strains in the population. Taking this viewpoint, you may say that some of these bans have no effect at all. But you would be ignoring a crucial detail.
In his Nobel prize speech, Fleming himself gave a warning about how mass underdosing could trigger the creation of antibiotic resistant strains, yet within ten years underdosing became standard practice within the agricultural industry.
It is crucial that we make sure that antibiotics are always used responsibly. The key reason why banning antibiotic growth promoters was that it was one demonstrable case in which antibiotics were used irresponsibly.
The other key problem with these bans is that no one knows the extent to which it will affect human health. It should prevent new strains of antibiotic resistant bacteria evolving on farms, such as livestock associated MRSA, or antibiotic resistant Enterococci.
However, expecting these bans to eliminate all antibiotic resistance is to unfairly place all of the blame on farming and agriculture for our current situation. The primary environment in which antibiotic resistant bacteria most commonly evolve, and where they are at their most dangerous, is found in hospitals. Any antibiotic resistance genes which have already made the jump into this environment are here to stay. Regulating antibiotic use in hospitals is difficult, because that is where we, as humans, need them the most. As much as we may worry about how the price of meat may be affected, if we cannot accept that relatively minor sacrifice, we will not be able to accept the changes and the costs needed to eradicate antibiotic resistance from our healthcare systems.
The genie of antibiotic resistance is out of the bottle, but it wasn't just Robert Stokstad who had a hand in releasing it. We may sneer at growth promoters because they are the worst example of how we have squandered antibiotics. We may lament at how some faceless evil within the agri-business made the calculation that our future is worth trading for cheaper meat today. But we all had a hand in shaking the genie out of its bottle. We still have a hand in determining our own future. Even those of us who currently live in Europe may soon be inundated with american meat raised antibiotic growth promoters if certain trade agreements are successful. They will once again be faced with the same choice facing everyone else in the world, the choice between a full stomach today or better health tomorrow.
References
The WHO's internal evaluation on the termination of antimicrobial growth promoters in Denmark
http://www.who.int/gfn/en/Expertsreportgrowthpromoterdenmark.pdf
Danish Pig production in a European Context
http://www.lf.dk/~/media/lf/Aktuelt/Publikationer/Svinekod/LFEUBenchUK110318.ashx
Cogliani C., Goossens H. & Greko C. (2011). Restricting Antimicrobial Use in Food Animals: Lessons from Europe, Microbe, 6 (6) 274-279. DOI:
Antibiotics & Agriculture Part 4: The Transfer of Antibiotic Resistance
The patient was in dire condition. A forty year old woman from Michigan, she had suffered badly from diabetes, kidney failure and a number of complications related to those diseases. Two years after she had started dialysis, disaster struck. She developed painful foot ulcers, and an infection in her leg that was so severe that the whole leg had to be amputated. What was worse was that immediately after the operation, her amputation wound became infected, with Staphylococcus aureus. In her only stroke of luck that day, the Staphylococcus aureus was susceptible to antibiotics. But the next year, the foot ulcers were back, and she required even more amputations, as well as treatments to prevent the bacterial infections causing these ulcers from becoming fatal.
The catheter that linked her blood to the hospital's dialysis machine, the replacement for her riven kidneys, provided Methicillin-Resistant Staphylococcus aureus with easy entry into her blood. There was only one antibiotic that could stop this MRSA infection. Vancomycin was given to the patient while the physicians removed the infected catheter. In its place, the physicians used a number of temporary catheters, to ensure that the patient could still use the dialysis machine.
But a number of these catheters also became infected. When the physicians examined these catheters, they realised that against all odds, things had taken a turn for the worse. They discovered that the Staphylococcus aureus on this catheter had been joined by Vancomycin resistant Enterococci. Now the Staphylococcus aureus were resistant to Vancomycin too. They searched all of the possible options that could have lead to this situation, and it was the DNA evidence that revealed what had happened. The Vancomycin resistant Enterococci, commonly found in the community but rarely infectious, had given its resistance genes to MRSA.
This was the first of a series of outbreaks of VRSA that occurred in Michigan, and all of them had a similar theme. A person with an MRSA infection would spontaneously develop full blown resistance to vancomycin out of nowhere. The only commonality in all of these cases was the presence of vancomycin resistant Enterococci both before and during these cases. So how did vancomycin resistant Enterococci pass along their resistance to MRSA ?
The answer lies with DNA molecules known as plasmids.
These are rings of DNA which can carry genes between different bacteria. The exchange of plasmids between bacteria is a key driver of bacterial evolution, as it allows species to share genes between eachother. They enable bacteria to acquire new traits from other bacteria in the vicinity, which can allow them to adapt to their environment in new ways. In this case, the vancomycin resistance "trait" was carried on a plasmid in Enterococci, and this plasmid could be very easily transferred to Staphylococcus aureus. The high abundance of Enterococci with vancomycin resistance increased the probability of this occurring.
This constant transfer of plasmids between bacteria plays a key role in their evolution. It allows a bacterium entering a new environment to steal some useful genes from the bacteria that are already there, helping it adapt to that niche. This is what happened in the cases discussed above, and is one of the more insidious methods through which antibiotic resistance can spread.
As we've seen in the previous posts, the unregulated use (and in some cases regulated use) of antibiotics in agriculture leads to the evolution of new resistant strains of bacteria. These strains can exchange this resistance using plasmids. The transfer of these plasmids to human pathogens is a major threat to human health.
Making things worse is that some plasmids can carry multiple resistance genes, rendering a variety of different antibiotics useless. The problem with using antibiotics in agriculture comes primarily from increasing the net amount of these non-pathogenic bacteria with resistance genes.
In the above case study, we have seen that Enterococci can exchange its resistance with Staphylococcus aureus. But we only know about Enterococci because on rare occasions, they can cause disease in humans. We don;t keep a track of all of the bacteria that don't cause disease. These are the bacteria that live in our bodies, that help us digest food and maintain an immune system. we are constantly exchanging these bacteria with our environmental surroundings.
They live under the radar, and nobody notices when they develop antibiotic resistance. Since they never cause disease in humans, we never need to prescribe antibiotics against them. The only time they would encounter sustained levels of antibiotics is on a farm, where they are constantly infused into the feeds of their animal hosts. Here they can evolve new resistances, and when they get transferred to humans, can exchange their antibiotic resistances with the bacteria they find in their new niche.
It is difficult for us to tell what kind of resistances an invading pathogen could potentially pick up from these bacteria.
To use an analogy, these silent bacteria may act as weapons merchants, hoarding resistances until the can share them with one of our potential enemies.
One way for researchers to investigate this is to simply take a snapshot of bacteria within an area, and just test for the resistance genes. Instead of looking for the weapons merchants, they are focussing on checking for the weapons.
With this technique, the scientists directly checked for the presence of resistance genes in an environment. This is known as the “resistome”.
Recently a group of researchers took it upon themselves to catalogue the “resistome” of three different countries. They compared the types of resistances they found in different countries to the way antibiotics were used in each of them.
The types of antibiotics that bacteria were resistant to were slightly different in each of the three countries they investigated (USA, Spain and Denmark). The antibiotics to which bacteria were most commonly resistant were the ones that were approved for use in animals. Antibiotic resistances were lowest in the places that had the ban in place for the longest time.
This all indicates that the agricultural use of antibiotics has contributed to the creation of a number of antibiotic resistant bacteria, but increased the number of resistance genes in our environment available for other pathogens to become resistant.
The mountain of evidence is indisputable. There is no doubt that new strains of antibiotic resistant bacteria owe their genesis to the reckless use of the drugs on farms. But is it fair for farms to take on the full brunt of the blame for the fall of antibiotics ? Would we not have antibiotic resistant bacteria in our hospitals even if the farms had banned them ?
I'll be dealing with this question in the conclusion of this series next time.
To be continued.....
References
Chang S., Sievert D.M., Hageman J.C., Boulton M.L., Tenover F.C., Downes F.P., Shah S., Rudrik J.T., Pupp G.R. & Brown W.J. & Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene., The New England journal of medicine, PMID: 12672861
Zhu W., Murray P.R., Huskins W.C., Jernigan J.A., McDonald L.C., Clark N.C., Anderson K.F., McDougal L.K., Hageman J.C. & Olsen-Rasmussen M. & (2010). Dissemination of an Enterococcus Inc18-Like vanA Plasmid Associated with Vancomycin-Resistant Staphylococcus aureus, Antimicrobial Agents and Chemotherapy, 54 (10) 4314-4320. DOI: 10.1128/AAC.00185-10
Forslund K., Sunagawa S., Kultima J.R., Mende D., Arumugam M., Typas A. & Bork P. (2013). Country-specific antibiotic use practices impact the human gut resistome., Genome research, PMID: 23568836
The catheter that linked her blood to the hospital's dialysis machine, the replacement for her riven kidneys, provided Methicillin-Resistant Staphylococcus aureus with easy entry into her blood. There was only one antibiotic that could stop this MRSA infection. Vancomycin was given to the patient while the physicians removed the infected catheter. In its place, the physicians used a number of temporary catheters, to ensure that the patient could still use the dialysis machine.
But a number of these catheters also became infected. When the physicians examined these catheters, they realised that against all odds, things had taken a turn for the worse. They discovered that the Staphylococcus aureus on this catheter had been joined by Vancomycin resistant Enterococci. Now the Staphylococcus aureus were resistant to Vancomycin too. They searched all of the possible options that could have lead to this situation, and it was the DNA evidence that revealed what had happened. The Vancomycin resistant Enterococci, commonly found in the community but rarely infectious, had given its resistance genes to MRSA.
This was the first of a series of outbreaks of VRSA that occurred in Michigan, and all of them had a similar theme. A person with an MRSA infection would spontaneously develop full blown resistance to vancomycin out of nowhere. The only commonality in all of these cases was the presence of vancomycin resistant Enterococci both before and during these cases. So how did vancomycin resistant Enterococci pass along their resistance to MRSA ?
The answer lies with DNA molecules known as plasmids.
These are rings of DNA which can carry genes between different bacteria. The exchange of plasmids between bacteria is a key driver of bacterial evolution, as it allows species to share genes between eachother. They enable bacteria to acquire new traits from other bacteria in the vicinity, which can allow them to adapt to their environment in new ways. In this case, the vancomycin resistance "trait" was carried on a plasmid in Enterococci, and this plasmid could be very easily transferred to Staphylococcus aureus. The high abundance of Enterococci with vancomycin resistance increased the probability of this occurring.
This constant transfer of plasmids between bacteria plays a key role in their evolution. It allows a bacterium entering a new environment to steal some useful genes from the bacteria that are already there, helping it adapt to that niche. This is what happened in the cases discussed above, and is one of the more insidious methods through which antibiotic resistance can spread.
As we've seen in the previous posts, the unregulated use (and in some cases regulated use) of antibiotics in agriculture leads to the evolution of new resistant strains of bacteria. These strains can exchange this resistance using plasmids. The transfer of these plasmids to human pathogens is a major threat to human health.
Making things worse is that some plasmids can carry multiple resistance genes, rendering a variety of different antibiotics useless. The problem with using antibiotics in agriculture comes primarily from increasing the net amount of these non-pathogenic bacteria with resistance genes.
In the above case study, we have seen that Enterococci can exchange its resistance with Staphylococcus aureus. But we only know about Enterococci because on rare occasions, they can cause disease in humans. We don;t keep a track of all of the bacteria that don't cause disease. These are the bacteria that live in our bodies, that help us digest food and maintain an immune system. we are constantly exchanging these bacteria with our environmental surroundings.
They live under the radar, and nobody notices when they develop antibiotic resistance. Since they never cause disease in humans, we never need to prescribe antibiotics against them. The only time they would encounter sustained levels of antibiotics is on a farm, where they are constantly infused into the feeds of their animal hosts. Here they can evolve new resistances, and when they get transferred to humans, can exchange their antibiotic resistances with the bacteria they find in their new niche.
It is difficult for us to tell what kind of resistances an invading pathogen could potentially pick up from these bacteria.
To use an analogy, these silent bacteria may act as weapons merchants, hoarding resistances until the can share them with one of our potential enemies.
One way for researchers to investigate this is to simply take a snapshot of bacteria within an area, and just test for the resistance genes. Instead of looking for the weapons merchants, they are focussing on checking for the weapons.
With this technique, the scientists directly checked for the presence of resistance genes in an environment. This is known as the “resistome”.
Recently a group of researchers took it upon themselves to catalogue the “resistome” of three different countries. They compared the types of resistances they found in different countries to the way antibiotics were used in each of them.
The types of antibiotics that bacteria were resistant to were slightly different in each of the three countries they investigated (USA, Spain and Denmark). The antibiotics to which bacteria were most commonly resistant were the ones that were approved for use in animals. Antibiotic resistances were lowest in the places that had the ban in place for the longest time.
This all indicates that the agricultural use of antibiotics has contributed to the creation of a number of antibiotic resistant bacteria, but increased the number of resistance genes in our environment available for other pathogens to become resistant.
The mountain of evidence is indisputable. There is no doubt that new strains of antibiotic resistant bacteria owe their genesis to the reckless use of the drugs on farms. But is it fair for farms to take on the full brunt of the blame for the fall of antibiotics ? Would we not have antibiotic resistant bacteria in our hospitals even if the farms had banned them ?
I'll be dealing with this question in the conclusion of this series next time.
To be continued.....
References
Chang S., Sievert D.M., Hageman J.C., Boulton M.L., Tenover F.C., Downes F.P., Shah S., Rudrik J.T., Pupp G.R. & Brown W.J. & Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene., The New England journal of medicine, PMID: 12672861
Zhu W., Murray P.R., Huskins W.C., Jernigan J.A., McDonald L.C., Clark N.C., Anderson K.F., McDougal L.K., Hageman J.C. & Olsen-Rasmussen M. & (2010). Dissemination of an Enterococcus Inc18-Like vanA Plasmid Associated with Vancomycin-Resistant Staphylococcus aureus, Antimicrobial Agents and Chemotherapy, 54 (10) 4314-4320. DOI: 10.1128/AAC.00185-10
Forslund K., Sunagawa S., Kultima J.R., Mende D., Arumugam M., Typas A. & Bork P. (2013). Country-specific antibiotic use practices impact the human gut resistome., Genome research, PMID: 23568836
Antibiotics & Agriculture Part 3: The Spread of Resistant Bacteria
The application of antibiotics to livestock has provided a boon to the agricultural industry. Unfortunately an outbreak of Salmonella showed that this application could have some untoward side effects. The farmers and veterinarians not only failed to contain this outbreak of Salmonella, but botched the antibiotic treatment so thoroughly that a multi-drug resistant strain of this pathogen emerged and spread to humans.
Such was the outcry in response to this outbreak that the government set up the Swann report, which attempted to promote more responsible usage of antibiotics. Even though the 1964 outbreak was primarily a result of improper medication for farm animals, the use of antibiotic growth promoters emerged as a specific concern. One of the sole achievements of this report was to separate the antibiotics used in humans to those used in animals, with specific restrictions on the use of antibiotic growth promoters.
Other countries experienced similar issues. An investigation in the US found that between 1971-1983, the majority of outbreaks of Multi-drug resistant Salmonella stemmed from contact with either farms or animal products. These antibiotic resistant Salmonella proved to be more lethal than their antibiotic sensitive counterparts. In 1977 the FDA decided that it was no longer safe to use certain antibiotics as growth promoters. They tried to stop front-line antibiotics such as penicillin and tetracycline being used as agricultural growth promoters. But for reasons that are unknown, they never followed up on their declarations. It is likely that the FDA simply didn't have the resources or the public support to pass such a law.
In contrast, Northern Europe had begun to implement restrictions on the usage of antibiotics in livestock. Often these restrictions consisted of allowing only one set of antibiotics for the agricultural industry and one for the medical community. But this soon encountered a major setback.
Clinicians began to encounter Vancomycin resistant strains of Enterococci. Vancomycin is often the drug of last resort, and was supposedly tightly regulated so as to prevent resistance developing. These outbreaks often occurred in hospitals, but not always. When doctors examined patients to find out where this bacterium was coming from, they found something surprising. The source of these Vancomycin resistant Enterococci infections originated from the community. The doctors redoubled their efforts to work out the source of this infection. They checked farm animals, food from shops, sewage outflows, and any other possible place where Enterococci could hide. What they found surprised them. They found this bacterium in farm animals and food sources and the sewage outflow. They found that not only were these hospital outbreaks traceable to these community sources, but there was a veritable reservoir of vancomycin strains out there that had not yet reached the hospital. But this presented a puzzle.
Vancomycin was only available to hospitals. In accordance with laws, the farms in the area were using different antibiotics. So why were these bacteria in the community, who should never have even seen Vancomycin, suddenly becoming resistant to it ?
The truth is that the bacteria had not specifically developed a resistance to Vancomycin. They had developed a resistance to a drug named Avoparcin. The vancomycin resistance was just a lucky side effect of this. You may not have heard of Avoparcin. This is because it was never meant to be used in humans. It was one of the few antibiotics allowed to be used as a growth promoter. What no-one had foreseen was that it's structure was so similar to vancomycin that it would breed resistance to it. And as a result, one of the key antibiotics to stop hospital outbreaks was rendered useless against the Enterococci.
But why should we worry about these bacteria. Enterococci aren't much of a threat outside of the hospital, and even then they tend not to have multiple drug resistances. Whilst we can worry about Salmonella, we should remember that the best ways of treating Salmonella don't require antibiotics at all. So why should the spread of these antibiotic resistant bacteria be a worry for us ?
To Be Continued.....
References
Holmberg S., Wells J. & Cohen M. (1984). Animal-to-man transmission of antimicrobial-resistant Salmonella: investigations of U.S. outbreaks, 1971-1983, Science, 225 (4664) 833-835. DOI: 10.1126/science.6382605
Bates J., Jordens J.Z. & Griffiths D.T. (1994). Farm animals as a putative reservoir for vancomycin-resistant enterococcal infection in man, Journal of Antimicrobial Chemotherapy, 34 (4) 507-514. DOI: 10.1093/jac/34.4.507
O'Brien T. (2002). Emergence, Spread, and Environmental Effect of Antimicrobial Resistance: How Use of an Antimicrobial Anywhere Can Increase Resistance to Any Antimicrobial Anywhere Else, Clinical Infectious Diseases, 34 (s3) S78-S84. DOI: 10.1086/340244
http://docs.nrdc.org/health/files/hea_12032301a.pdf
Such was the outcry in response to this outbreak that the government set up the Swann report, which attempted to promote more responsible usage of antibiotics. Even though the 1964 outbreak was primarily a result of improper medication for farm animals, the use of antibiotic growth promoters emerged as a specific concern. One of the sole achievements of this report was to separate the antibiotics used in humans to those used in animals, with specific restrictions on the use of antibiotic growth promoters.
Other countries experienced similar issues. An investigation in the US found that between 1971-1983, the majority of outbreaks of Multi-drug resistant Salmonella stemmed from contact with either farms or animal products. These antibiotic resistant Salmonella proved to be more lethal than their antibiotic sensitive counterparts. In 1977 the FDA decided that it was no longer safe to use certain antibiotics as growth promoters. They tried to stop front-line antibiotics such as penicillin and tetracycline being used as agricultural growth promoters. But for reasons that are unknown, they never followed up on their declarations. It is likely that the FDA simply didn't have the resources or the public support to pass such a law.
In contrast, Northern Europe had begun to implement restrictions on the usage of antibiotics in livestock. Often these restrictions consisted of allowing only one set of antibiotics for the agricultural industry and one for the medical community. But this soon encountered a major setback.
Clinicians began to encounter Vancomycin resistant strains of Enterococci. Vancomycin is often the drug of last resort, and was supposedly tightly regulated so as to prevent resistance developing. These outbreaks often occurred in hospitals, but not always. When doctors examined patients to find out where this bacterium was coming from, they found something surprising. The source of these Vancomycin resistant Enterococci infections originated from the community. The doctors redoubled their efforts to work out the source of this infection. They checked farm animals, food from shops, sewage outflows, and any other possible place where Enterococci could hide. What they found surprised them. They found this bacterium in farm animals and food sources and the sewage outflow. They found that not only were these hospital outbreaks traceable to these community sources, but there was a veritable reservoir of vancomycin strains out there that had not yet reached the hospital. But this presented a puzzle.
Vancomycin was only available to hospitals. In accordance with laws, the farms in the area were using different antibiotics. So why were these bacteria in the community, who should never have even seen Vancomycin, suddenly becoming resistant to it ?
The truth is that the bacteria had not specifically developed a resistance to Vancomycin. They had developed a resistance to a drug named Avoparcin. The vancomycin resistance was just a lucky side effect of this. You may not have heard of Avoparcin. This is because it was never meant to be used in humans. It was one of the few antibiotics allowed to be used as a growth promoter. What no-one had foreseen was that it's structure was so similar to vancomycin that it would breed resistance to it. And as a result, one of the key antibiotics to stop hospital outbreaks was rendered useless against the Enterococci.
But why should we worry about these bacteria. Enterococci aren't much of a threat outside of the hospital, and even then they tend not to have multiple drug resistances. Whilst we can worry about Salmonella, we should remember that the best ways of treating Salmonella don't require antibiotics at all. So why should the spread of these antibiotic resistant bacteria be a worry for us ?
To Be Continued.....
References
Holmberg S., Wells J. & Cohen M. (1984). Animal-to-man transmission of antimicrobial-resistant Salmonella: investigations of U.S. outbreaks, 1971-1983, Science, 225 (4664) 833-835. DOI: 10.1126/science.6382605
Bates J., Jordens J.Z. & Griffiths D.T. (1994). Farm animals as a putative reservoir for vancomycin-resistant enterococcal infection in man, Journal of Antimicrobial Chemotherapy, 34 (4) 507-514. DOI: 10.1093/jac/34.4.507
O'Brien T. (2002). Emergence, Spread, and Environmental Effect of Antimicrobial Resistance: How Use of an Antimicrobial Anywhere Can Increase Resistance to Any Antimicrobial Anywhere Else, Clinical Infectious Diseases, 34 (s3) S78-S84. DOI: 10.1086/340244
http://docs.nrdc.org/health/files/hea_12032301a.pdf
#MicroTwJC : The Creation of a Superbug
The year was 2004. The patient was a 6 month old baby girl. She was about to enter thoracic surgery, when the doctors found that she was harbouring methicillin resistant Staphylococcus aureus. Now, in most western hospitals, the origin of this bacterium would not be a mystery. But this was a hospital based in the Netherlands. The Dutch have a "search and destroy" mentality when it comes to dealing with superbugs, and have been very successful at keeping their hospitals free of MRSA. They wanted it to stay that way. They had to find the source of this MRSA, and put a stop to it. The hospital equipment was scrutinised for any traces of the bacterium. None could be found.
They eliminated the MRSA from the baby, and then sent her home with her parents. But when they followed up, the baby was once again colonised with MRSA. They went through the same process again and again, until they realised that the baby was continuously being re-infected with the bacterium from an unknown source. The doctors found that the babies parents were also carriers of MRSA. but where did they get the disease from ? If it wasn't coming from the hospital, then where was it coming from ?
It turned out that the family lived on a farm raising pigs. The pigs were tested. They were the source of the MRSA.
Other pigs on different farms in that area also carried this strain of MRSA. A number of other cases of farmers and vets catching MRSA off their pigs. They concluded that farmers were 760x more likely to get an MRSA infection than any other Dutch people. Further research revealed that 39% of pigs entering a slaughterhouse carried MRSA. Hospitals in close proximity to pig farms tended to see more patients with MRSA than hospitals that were far from pig farms. This MRSA appears to be different from the hospital associated MRSA's we are more familiar with. It is primarily carried by pigs, and was a leading cause of MRSA infection in the Netherlands.
So now we know that pigs can carry MRSA, it is time to ask an important question. How did they get MRSA ? How did this particular strain evolve ? These are the questions that this weeks #MicroTwJC paper aims to answer.
They eliminated the MRSA from the baby, and then sent her home with her parents. But when they followed up, the baby was once again colonised with MRSA. They went through the same process again and again, until they realised that the baby was continuously being re-infected with the bacterium from an unknown source. The doctors found that the babies parents were also carriers of MRSA. but where did they get the disease from ? If it wasn't coming from the hospital, then where was it coming from ?
It turned out that the family lived on a farm raising pigs. The pigs were tested. They were the source of the MRSA.
Other pigs on different farms in that area also carried this strain of MRSA. A number of other cases of farmers and vets catching MRSA off their pigs. They concluded that farmers were 760x more likely to get an MRSA infection than any other Dutch people. Further research revealed that 39% of pigs entering a slaughterhouse carried MRSA. Hospitals in close proximity to pig farms tended to see more patients with MRSA than hospitals that were far from pig farms. This MRSA appears to be different from the hospital associated MRSA's we are more familiar with. It is primarily carried by pigs, and was a leading cause of MRSA infection in the Netherlands.
So now we know that pigs can carry MRSA, it is time to ask an important question. How did they get MRSA ? How did this particular strain evolve ? These are the questions that this weeks #MicroTwJC paper aims to answer.
Antibiotics & Animals Part 2: The First Warnings
In the previous post, we were wowed by the miraculous discovery that antibiotics could improve the growth and well being of farmed animals, such as pigs and baby chicks. The use of these growth promoters enabled farmers to save money on animal feed and improve the health of their animals. Soon, nearly 50% of all antibiotic sales went to the agricultural industry. Whilst there were some concerns over this unregulated use triggering the development of antibiotic resistant bacteria, without evidence these fell on deaf ears. This would soon change.
We begin this chapter of the story at the Enteric Reference laboratory. The job of this reference laboratory was to receive and catalogue samples of bacteria obtained from intestinal infections occurring around the country. It was during the 1960's that they began to receive samples from concerned farmers.
The environments on intensive farms of this era could best be described as overcrowded factories for disease. The farmers had noticed that calves were particularly prone to getting diarrhoeal infections. The bacteria causing these infections was Salmonella typhimurium, the bacterium responsible for human typhoid disease. This was not only a threat to the health of the herd, and those who interacted with them. Calves were dying. The Salmonella outbreaks needed to be brought under control. This is where it all started to go wrong.
There were two methods that were used to put a stop to Salmonella on these farms. The first method was to use high doses antibiotics to treat visibly sick cattle. The second method was to give lower doses of antibiotics to the rest of the visibly healthy herd, to prevent them getting ill. I say "visibly" because cows can carry Salmonella without showing any symptoms, so it is likely that plenty of the cows with Salmonella received the lower doses of antibiotic.
Unbeknownst to the veterinarians, they were creating the perfect environment for bacteria to develop resistance.
Antibiotic resistant strains began to make their first appearance in the beginning of 1963, when a strain developed resistance to sulfonamides and streptomycin. A year later these bacteria had become resistant to six more antibiotics.
Soon, this multi-resistant strain of Salmonella began to spread to humans. The Enteric reference laboratory received over 500 samples of this same bacterial strain, obtained from human infections. The antibiotics that would normally used in these situations turned out to be useless. This outbreak provided dramatic evidence of the hazards of utilising antibiotics in agriculture. The UK government was forced into action
In 1969, the Swann committee convened to change the way we used antibiotics, so that this kind of outbreak would never be repeated. They recommended that a quasi-non governmental organisation (Quango) be created, which would act to oversee the use of antibiotics for both humans and animals. It was there to increase transparency, to make sure that people knew what antibiotics were being used for, and how much they were used. It would bring together the usage of both veterinary and medical antibiotics under one authority. This co-ordination would enable scientists to better understand the threat of resistance in all of its facets.
Whilst the committee’s job was to regulate the use of antibiotics in both humans and animals, it ran into a number of problems. But the various different interest groups involved in antibiotics had no compulsion to co-operate. The committee had no real power to control the use of antibiotics, nor did it have any resources to investigate the impact of antibiotic overuse. Eventually it died a quiet death, having never quite lived up to the promise of its birth.
To be Continued NextTuesday... Thursday...
Anderson E.S. (1968). Drug Resistance in Salmonella Typhimurium and its Implications, BMJ, 3 (5614) 333-339. DOI: 10.1136/bmj.3.5614.333
(1981). Death of a quango., BMJ, 282 (6274) 1413-1414. DOI: 10.1136/bmj.282.6274.1413-a
http://www.guardian.co.uk/society/2006/mar/22/health.science
We begin this chapter of the story at the Enteric Reference laboratory. The job of this reference laboratory was to receive and catalogue samples of bacteria obtained from intestinal infections occurring around the country. It was during the 1960's that they began to receive samples from concerned farmers.
The environments on intensive farms of this era could best be described as overcrowded factories for disease. The farmers had noticed that calves were particularly prone to getting diarrhoeal infections. The bacteria causing these infections was Salmonella typhimurium, the bacterium responsible for human typhoid disease. This was not only a threat to the health of the herd, and those who interacted with them. Calves were dying. The Salmonella outbreaks needed to be brought under control. This is where it all started to go wrong.
There were two methods that were used to put a stop to Salmonella on these farms. The first method was to use high doses antibiotics to treat visibly sick cattle. The second method was to give lower doses of antibiotics to the rest of the visibly healthy herd, to prevent them getting ill. I say "visibly" because cows can carry Salmonella without showing any symptoms, so it is likely that plenty of the cows with Salmonella received the lower doses of antibiotic.
Unbeknownst to the veterinarians, they were creating the perfect environment for bacteria to develop resistance.
Antibiotic resistant strains began to make their first appearance in the beginning of 1963, when a strain developed resistance to sulfonamides and streptomycin. A year later these bacteria had become resistant to six more antibiotics.
Soon, this multi-resistant strain of Salmonella began to spread to humans. The Enteric reference laboratory received over 500 samples of this same bacterial strain, obtained from human infections. The antibiotics that would normally used in these situations turned out to be useless. This outbreak provided dramatic evidence of the hazards of utilising antibiotics in agriculture. The UK government was forced into action
In 1969, the Swann committee convened to change the way we used antibiotics, so that this kind of outbreak would never be repeated. They recommended that a quasi-non governmental organisation (Quango) be created, which would act to oversee the use of antibiotics for both humans and animals. It was there to increase transparency, to make sure that people knew what antibiotics were being used for, and how much they were used. It would bring together the usage of both veterinary and medical antibiotics under one authority. This co-ordination would enable scientists to better understand the threat of resistance in all of its facets.
Whilst the committee’s job was to regulate the use of antibiotics in both humans and animals, it ran into a number of problems. But the various different interest groups involved in antibiotics had no compulsion to co-operate. The committee had no real power to control the use of antibiotics, nor did it have any resources to investigate the impact of antibiotic overuse. Eventually it died a quiet death, having never quite lived up to the promise of its birth.
To be Continued Next
Anderson E.S. (1968). Drug Resistance in Salmonella Typhimurium and its Implications, BMJ, 3 (5614) 333-339. DOI: 10.1136/bmj.3.5614.333
(1981). Death of a quango., BMJ, 282 (6274) 1413-1414. DOI: 10.1136/bmj.282.6274.1413-a
http://www.guardian.co.uk/society/2006/mar/22/health.science
Antibiotics & Agriculture Part 1: The Discovery of Growth Promoters
This story begins with Robert Stokstad, an agricultural scientist brought up on a Californian poultry farm . He had started his career fighting against malnutrition in chicks. He had found that a haemorraghic disease in chicks was in fact caused by malnutrition. He had followed this up by examining the diet of baby chicks, to work out which parts of the diet are the most essential, and which of those, if neglected could lead to disease. He was one of the first to discover that folic acid is an important component of nutrition in chicks, before people realised it’s importance for humans.
It was at Lederle pharmaceuticals, whilst working with Thomas Juke, that he made another significant discovery about the right things to feed baby chicks. He had found during his work that feeding chicks a diet of vegetables alone was not enough. In fact, many chicks would end up dying on this diet. If they were to survive, then some degree of animal protein was needed. Other people working in his field had found that adding a small amount of “sardine meal” to the mix helped this. But then in a later paper, those same researchers, Hammond and Titus, found that mixing in cow manure produced a similar effect. Yes, you read that right, there were people feeding chicks cow manure, and found that it was more healthy than feeding them a diet of just vegetables.
It was known at the time that vitamin B12 was a key factor needed for chicks to grow, and that often the vegetable diets given to these chicks did not have enough of it. So Stokstad and Juke fed the chicks different mixtures of foods, and looked at how well they grew afterwards. One of the foods they included was a bacterium, Streptomyces aureofaciens, which they grew up and dried out and added to the feeds of the chicks. This was to work out why the cow manure turned out to be such a great dietary supplement. Stokstad knew that manure is full of bacteria, and that bacteria could produce B12. So the reason that cow manure was good for chicks was that it was a source of B12.
But Stokstad was not the sort to rule anything out. He decided to compare the potency of Streptomyces aureofaciens against B12 purified from liver extract. He found that the purified liver extract improved the growth of the chicks, nearly doubling their final weight. But when he fed the chicks Streptomyces aureofaciens , he discovered that they grew far faster and bigger than the ones fed with just the liver extract. This growth spurt was about more than vitamin B12. Streptomyces aureofaciens was producing something else that was boosting the growth of these chicks. So what was this mysterious factor which made these chicks grow up so well ?
It was a compound known then as aureomycin, and it was amongst the first tetracycline antibiotics ever discovered. It was also one of the first antibiotic growth promoters. Other researchers were also beginning to discover the benefits of antibiotics in promoting the growth of animals. The use of antibiotics as feed additives caught on like wildfire.
One of the first to express their concerns over the growth of this industry was Robert Wrigglesworth, who in 1952 wrote a letter to the British Medical Journal
To Be Continued.....
References
STOKSTAD E.L.R. & JUKES T.H. (1949). The multiple nature of the animal protein factor., The Journal of biological chemistry, PMID: 18135798
Shane B. & Carpenter K. (1997). E. L. Robert Stokstad, Journal of Nutrition, (127) 199-201. DOI:
Wigglesworth R. (1952). Value of Organic Manures, BMJ, 1 (4772) 1357-1358. DOI: 10.1136/bmj.1.4772.1357-c
It was at Lederle pharmaceuticals, whilst working with Thomas Juke, that he made another significant discovery about the right things to feed baby chicks. He had found during his work that feeding chicks a diet of vegetables alone was not enough. In fact, many chicks would end up dying on this diet. If they were to survive, then some degree of animal protein was needed. Other people working in his field had found that adding a small amount of “sardine meal” to the mix helped this. But then in a later paper, those same researchers, Hammond and Titus, found that mixing in cow manure produced a similar effect. Yes, you read that right, there were people feeding chicks cow manure, and found that it was more healthy than feeding them a diet of just vegetables.
It was known at the time that vitamin B12 was a key factor needed for chicks to grow, and that often the vegetable diets given to these chicks did not have enough of it. So Stokstad and Juke fed the chicks different mixtures of foods, and looked at how well they grew afterwards. One of the foods they included was a bacterium, Streptomyces aureofaciens, which they grew up and dried out and added to the feeds of the chicks. This was to work out why the cow manure turned out to be such a great dietary supplement. Stokstad knew that manure is full of bacteria, and that bacteria could produce B12. So the reason that cow manure was good for chicks was that it was a source of B12.
But Stokstad was not the sort to rule anything out. He decided to compare the potency of Streptomyces aureofaciens against B12 purified from liver extract. He found that the purified liver extract improved the growth of the chicks, nearly doubling their final weight. But when he fed the chicks Streptomyces aureofaciens , he discovered that they grew far faster and bigger than the ones fed with just the liver extract. This growth spurt was about more than vitamin B12. Streptomyces aureofaciens was producing something else that was boosting the growth of these chicks. So what was this mysterious factor which made these chicks grow up so well ?
It was a compound known then as aureomycin, and it was amongst the first tetracycline antibiotics ever discovered. It was also one of the first antibiotic growth promoters. Other researchers were also beginning to discover the benefits of antibiotics in promoting the growth of animals. The use of antibiotics as feed additives caught on like wildfire.
One of the first to express their concerns over the growth of this industry was Robert Wrigglesworth, who in 1952 wrote a letter to the British Medical Journal
We have the prospect of more antibiotics being sold in the USA, as growth promoters for food in farm animals than are used for clinical medicine.But at the time, these kinds of concerns were brushed aside, with some justification. So what if the bacteria that infect livestock become slightly resistant to antibiotics ? The bacteria that live within pigs and chicken don’t pose a problem to the health of people, because the only time that those aforementioned bacteria could possibly come into contact with us is after being thoroughly cooked. Right ?
To Be Continued.....
References
STOKSTAD E.L.R. & JUKES T.H. (1949). The multiple nature of the animal protein factor., The Journal of biological chemistry, PMID: 18135798
Shane B. & Carpenter K. (1997). E. L. Robert Stokstad, Journal of Nutrition, (127) 199-201. DOI:
Wigglesworth R. (1952). Value of Organic Manures, BMJ, 1 (4772) 1357-1358. DOI: 10.1136/bmj.1.4772.1357-c
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