A History of Infection

The little things that have altered history every step of the way.

The curious case of Dr. Pettenkofer

I want you to come back in time with me to the end of the 19th century. Science was becoming increasingly important in people’s daily lives and it had a lot to say about almost every aspect of life. Cities had grown massively in the past 100 years thanks to the products of the industrial revolution, which were fueled by the application of science. Cogs and belts whizzed and steel lurched to preform the work of a 1000 horses. But something else lurks in the shadows; there are dreadful unknown killers abound. Coughing, wheezing and the sounds of people groaning can be heard as they die slowly throughout the cities. Contagious diseases wrought havoc and destruction on the lives of people all over Europe.

Two of the main ideas about what was causing the increase in disease rates were hotly debated. Infection via organism like bacteria or Miasma (dirty air) which suggested that filth and dirt caused illness. We now know that contagious diseases are caused by viruses and bacteria; but naturally at some point people didn’t know what was the cause of disease. The miasma theory of infection had been wildly accepted for many centuries and took some of sciences best minds to demonstrate that it was incorrect. In fairness which would make more sense to you, that unimaginably small things that you have never seen and can’t see (with out very special equipment) can get inside your body and make you unwell or that things that look and smell bad have a way of passing on their quality of badness on to you. Miasma is still found in our use of language as well, we say to small children that things are dirty or unclean when what we really mean is that certain things might harbor vicious bacteria!

So we had two competing hypothesis and what is the best way to deal with two competing ideas? Do an experiment! The main two players in this story I wish to share, are a one Dr Koch who biology students know from, and giggle at, Koch’s postulates and the singular Dr Pettenkofer who very few biology students know about. This should give you some idea of who was routing for which idea! But there is a twist! During the end of the 19th century on the verge of an outbreak of Cholera in Hamburg which Koch was suggesting based on carful observation and statistical analysis. He even purported that a certain bacteria Vibrio cholerae (which had been independently discovered nearly 30 years earlier) was responsible for Cholera. While Pettenkofer was convinced that the outbreak was due to the high levels of pollution in the city and that infection require 3 separate conditions an x,y and and only when all 3 were present could Vcholeraebecome poisonous. In a way he was right, the pollution allowed for effective transmission of the bacteria but Pettenkofer was of a mind to try prove his point of a tirade of infection and in a big way!

Everyone looked like they did magic in the 19 century

Pettenkofer wrote to Koch and requested he send him a sample of his newly identified bacteria something which microbiologist still do these days. Once Pettenkofer received it, he had an experiment which he thought would prove his point; he was going to drink it! If Koch was right that Cholera was caused by the ingestion (fecal to oral) of this bacteria, then by drinking large amounts of it he would surely get Cholera. So he, a colleague and independent witnesses neutralised his stomach acid (removing this as a factor) and administered the vial of Vcholerae. Pettenkofer learnt something from this, that the V. choleraebacteria did not cause Cholera. All that happened was he felt a little unwell. He certainly did not get Cholera! Pettenkofer thought that this disproved the germ theory of disease. Quite rightly too, he took all the correct precautions to remove any bias from his self experiment.

Koch also spent time trying to develop psychic powers

A little back ground of Cholera may be needed at this point, it is caused by the bacteria Vibrio cholerae, as few as 10 Colony forming units (CFUs are the living and healthy bacteria) are capable of infecting a healthy person. Pettenkofer drank as many as a billion CFU’s! V. cholerae releases a toxin which alters how cells hold on to water leading to horrific diarrhea. One of the only real treatments is fluid replacements. Cholera is still deadly and a big problem in confounding issues like earthquakes and other natural and manmade disasters.

So the question is how did Pettenkofer survive or at least come out with his trousers clean! Allow me to put forward my own pet theory, V. cholerae has a interesting life style. It is highly infection at low levels. Once the level of V. cholerae bacteria builds up in an infected person a change occurs in the biology of the bacteria. Instead of becoming more virulent (how sick a bacteria makes you) V. cholerae turns off its virulence; it shuts down its toxin production and turns on its little out board motor known as flagellum and swims off down stream off to infect another person. I’ve mentioned this process before, its known as quorum sensing. Bacteria release a small molecule into the environment (soil, petri dish or intestines), they use these molecules as a census in which they chose how to act as a group. Most bacteria, to our knowledge, use these molecules, and many use it in order to work out when to become virulent. V. cholera however works the other way around; it counts these votes and when a certain level is reached it turns off its virulence.

So Pettenkofer could have survived by this little biological trick. If the V. cholerae he drank was at a high enough density its virulence would have been turned off leading to it just passing right through him. If he hadn’t played fair and had failed to neutralised his stomach acid then he might have become fully infected and suffered greatly at his own self experiment or at the very least would have required a new pair of trousers.

So what became of Pettenkofer, his results were largely ignored and moved into obscurity after some very good work promoting hygiene. Koch had just been consulted on a new water system for the city of Munich. In the city there were certain streets where one side had their water supplied by the newly designed water system, developed by Koch which could filter out the V. cholerae, while on the other side of the street water came from the Vcholerae infused local stream. This lead to situations where one side of some streets had Cholera while the new water system side was clear of Cholera. Pettenkofer carried on working in to his old age until depression took over and he ended his own life alone one evening. Koch isolated the bacterium that causes TB, discovered a way to isolate anthrax from blood samples, rediscover the Vibrio cholera and went on to win the Noble prize in 1905 for “his investigations and discoveries in relation to tuberculosis”.

Although Pettenkofer was wrong about his idea which could only have been confounded by his positive results disproving the germ theory I greatly admire his bravery. Even knowing in far greater detail then either man knew of bacteria in their days, I would never dream of drinking a vial of live V. cholerae. Pettenkofer’s principles of testing his ideas is the foundation on which Science progresses and we should, for at least that, recognise him.

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Why study english

Recently at a meeting concerning the history of infection collaboration Christina mentioned that a lot of people do not see the value in what they do. I must stick my hand high in the air and say; first, sorry. I have at one stage been that insufferable twerp who would have (have) asked that exact same question. But it got me thinking that I get the same question asked of me and I don’t think it is unquie to the humanities.

The question I find myself being asked is

“Why don’t you work on curing cancer or getting rid of HIV?”

To me this is the same question the humanities find themselves facing, essentially what is the value of what you do? I think now this is a woefully bad question.

My first response to this sort of inquest is ‘I do not find topic X as interesting as what I’m doing.’ Don’t get me wrong cancer and HIV are both really interesting things and topics and I commend anyone who works on them. But to me they are not as cool as looking at how a pathogens are shaped by the blind forces or evolution by our own doing and the beautiful elegance of natural selection.

But this is possibly not the best answer…

There exist a not particularly hidden scoffing culture of the humanities within the science. Some would call it a soft subject and rank it lower then the sciences and maths. But what does this mean? Soft? I think that it means things which can not be empirically tested. Now I love me some empirical testing but it is not the be all and end all. It might one day be but I can’t say for sure.

The study of language and literature can give us a breath taking insight into the human mind. It for one is the best way I know of that allows us to share a common narrative. This allows us the sense that we are the same human minds have the Same patterns and same feeling. In a phrase it allows us to see out of the minds eye of others.

For myself who doesn’t believe in deities or other higher powers I feel I have learnt a lot of my morals from this common minds eye. This is probably the same for a lot of people even those who think their morals come from religion.

Studying literature and having to defend this study is in some way similar to enjoying fine music and having to defend that. Now many people don’t enjoy many different forms of music. But I don’t think there is any better music. Aside from fabricated stories behind music in the form of manufactured pop in order to sell more records. Any way to sum up I believe that studying English or any humanities has value, a direct value to us all it brings us our past and gives us a point at which to sail at for the future by understanding who and what we are.

J

It’s been a while

We’ll so much for the noble plans to update this regularly. The main reason is a lack of access to editing this site at work. However I’m dedicated not to let this stop me. So let’s have an update.

First, I’m talking at phdpub soon, 14th of May.

Second, the league of nerds podcast is back into full swing.

Third, I’m finishing my PhD soon so I’m busy working on my thesis.

Finally, I’ve been throwing around some ideas about virulence and what it means for opportunistic pathogens.

In short when we think about pathogens we can talk about the fitness of those pathogens. Is it right to think of opportunistic pathogens as fit? A true pathogen is required to transmit in order to have a fitness. Opportunistic pathogens do not tend to transmit as a product of their virulence.

Virulence is typically a by-product of transmission but in a opportunistic pathogen virulence is not a function of transmission.

Food for thought at the moment.

J

Update

So here is the news I didn’t tell you about last time. So I’ve been talking to a number of people in recent months the most important of these are Freya Harrision and Cristina Lee in this story. Between the two of them they have been trying to setup a cross discipline research group looking at how disease and health were perceived in ancient times, how they treated disease and how did pathogen spread through these populations. I hopefully don’t need to tell you how excited I am to be involved in this collaboration.

So what will we be doing? Well that hasn’t yet been formalised but certainly one thing we plan on sorting out it getting someone in to the lab to test some of the medicines that we have quite accurate accounts of. I’m still trying to push to test the ‘potion’ to help with unruly dwarfs but it is probably best we stick to microbes.

Another side that I am very interested in seeing if we can get off the ground is how did pathogens spread through populations. There are a number of differences between population structures from today to the pre industrial age. These differences could have huge implications for how and why pathogens managed to cause such havoc. We have also wrangled a climate geologist. Together we could model climate and population and see if there is a link between plagues and climate.

I also hope that we can include some out reach into the project, currently we are talking about public lectures in 2015 but I don’t see why blogs like this and maybe even some youtube videos can’t find their way into the project.

There is one big problem so far and that is we haven’t secured funding but we are hopeful, mainly as this is truly a cross-disapline project and the university is always trying to get us to talk together and be friends.

So that is that for now, hopefully as the project develops I can let you all into more and more details and oh so juicy science.

 

The League of Nerds is on iTunes

What is a history of infection?

The project started in 2012 some time in September, I had wanted to get back into making YouTube videos but I didn’t want to make one like I used too. These were rebuttals to creationist and creationism. One, they could be very boring! Two, having to sit through and watch endless terrible videos on why I hate a God I do not believe in or have no morals became very dull. Three, others had said everything I could say and better.

So I decided I would stay clear of those, several month earlier I had written a piece on the history of Stds for the university newspaper and I really enjoyed telling people about these pathogens in, what I hope was an entertaining manner.

Now a year later and although I’m having to take a break to finish my PhD I think I have done some nice work and have improved the style a reasonable amount. At the same time hopefully the idea might find a home in a very similar project I’m involved with, more about that later.

So what is a history of infection? It is a way to communicate and sneak in complex microbiology and evolutionary principles into peoples minds in the guise of history. On a similar note of ulterior motives writing a blog, I hope will in some way improve my quite frankly shocking english. If it wasn’t for spellcheck it wouldn’t be just my grammar that is terrible. It should also be noted that I am not a historian, I am a microbiologist, and if I have learnt anything from making the videos it is that my interpretation of history is very shallow. This is one of the main issue I plan on addressing. The name, I did not want to call it History of infection as that implies a complete history. A history is my history, the stuff and sundry that I find interesting and hope in some way I can communicate to you too.

So what can you expect from this blog?

1. Microbiology smuggled into you brain.

2. Interesting analysis of research looking at how pathogens spread through population.

3. Bad Grammar and occasional bad spelling.

4. Updates of the hopefully long term plans to carry on doing something similar with the project in a professional manner.

So in the next update I hope I will have some news which I’m quite excited about but we will have to see if it works out or not. I’ll tell you either way!

Till then

Best wishes.

James

First cause

So I thought I’d take a trip down memory lane and show you all the first prototype history of infection.

I wrote an article for the university newspaper about the history of STDs. Some of you might notice similar themes to the valentines episode of the youtube video as I used this article as a script for that! 

Writing this piece I found that I really enjoyed writing and finding out the history of pathogens and thus A history of infection was born! 

February, the month of love; love has a different meaning in the biological world. As you will see in the magazine’s Valentine Special, it can be broken down into brain chemistry and animal instincts. To the microbiologist, however, it also conjures up images of sexually transmitted diseases (STDs). It does in my mind at least, which may go some way to explain why I’m often not invited out to dinner. So for the loveliest time of the year, I’ll give you all a short history of the microbes and viruses that make themselves at home in our naughty parts. Beware. This might just turn you celibate.

When most people think of STDs, they tend to think of HIV or the much more common Chlamydia. We also often assume that STDs are a 20th century problem, originating from the hedonistic heyday of the 60s. But as long as man has had dangly bits and enjoyed using them, there have been vermin that have hitched a ride.

Prior to the invention of antibiotics, venereal diseases were a big problem. Epic poems were written about STDs as plagues from the Gods visited upon disloyal followers and blasphemers. Some were also far more deadly then we think of them today. Syphilis is a prime example. Nowadays, syphilis is by no means a pleasant experience, but in comparison to the symptoms from a few hundred years ago, we seem to have it rather easy. For example: today most cases of syphilis present as single lesions that aren’t particularly painful or itchy. Now compare that to the historic syphilis where your face might “slough off”. One writer portrays a person with syphilis as “having boils that covered him from knee to head, causing flesh to fall from his face”. These boils were not small pimple-sized lesions but could grow to around the size of a cricket ball.

The emergence of syphilis is hotly debated, but here’s what we think we know. The first well recorded cases of syphilis hail from the 15th century during a French besiegement of Naples. However, examination of some remains found in Pompeii show clear signs of a syphilis-like disease that occurred much earlier. These remains date back to AD79. Some argue that syphilis was a disease bought back from the new world, since its appearance coincides with the “discovery” of the Americas. This would be, in some way, poetic justice as travellers to the new world wrought death on epic proportions from the diseases they and their animals brought (small pox and measles to name just a few).

It was estimated that in the 16th century, around one million people in Europe had syphilis; which works out as roughly 1 in 40 people having the disease. But that number would naturally vary depending on the location, being far higher in the urban centres. Soon after this time (17th century) syphilis began to decline in virulence. It no longer manifested itself as a whole body condition and began to resemble its modern day version. Why syphilis has become less severe is a bit of a mystery, but it can still be a killer today. In cases of Neuro-syphilis, the spirochetes (the bacteria responsible for the disease) begin to feast on your brain. Clearly a bacterium chomping away at your gray matter is something of an issue!

Syphilis has gone by many names and has often had some sort of racial nomenclature. For example, the Italians, Polish and Germans called syphilis the French disease. The Dutch called it the Spanish disease. The Russians called it the Polish disease. The Turks called it the Frank or Christian disease. And for some odd reason the Tahitians (a group of islands about 2000 miles northeast of New Zealand) called it the British disease.

Historically, treatments for syphilis have been almost as bad as the disease itself. The phrase “a night in the arms of Venus leads to a life time on mercury” gives us a strong hint as to one of the most popular treatments of the time: Mercury. Mercury was either applied directly, ingested, injected or, perhaps my favourite, fumigated. Fumigation of the body was used to treat many aliments. Galen suggested schizophrenia in women should be treated by fumigation of the vagina, but fumigating mercury was probably the least effective way of delivering mercury into the body. Nevermind that the treatment was not overly effective, mercury is one of the most toxic natural substances that we know of. Other treatments did exist; the most effective probably would have been the use of wild pansy, which has subsequently been shown to have some antimicrobial properties. Still, none one of these treatments were as efficient as the first antibiotics.

Although the first modern antibiotic, penicillin, was not discovered until 1928, an arsenic containing drug developed in 1908 was highly effective at treating early stage infections. Of course, as with the case of using mercury, one has to question the effectiveness of a deadly toxin to treat the disease, but it worked. Another brilliantly bizarre treatment for syphilis was founded on the notion that some people, who had developed high fevers from other conditions, had been cured of their syphilitic infection. So in order to give syphilis patients a high fever, they were infected with Malaria. The Malaria would induce a massively high fever and night sweats which would essentially cook off the syphilis. The Malarial infection would then later be treated with quinine. It’s important to note that this was not some “quack” treatment; this treatment strategy won its inventor, Julius Wagner-Jauregg, the noble prize in 1927.

Another interesting time in the history of STDs were the first and second world wars. Here was an era when young virile soldiers were sent away from home into foreign countries. As they were men, they tended to try and have sex with anything that is willing or at least not overly reluctant. Naturally, a soldier who has succumbed to venereal disease is not going to be of much use on the battle field, or at least be at a diminished capacity. The army essentially did not want its privates to be ineffective.

During this time, the war office invested a lot into the soldier’s having an understanding of how sexually transmitted diseases are spread. This effort was mainly in the form of training videos and posters depicting a femme fatale with stern warnings. However, it is an urban myth that some went a bit further and actually tried to blunt the troop’s libido by having rations laced with anti-aphrodisiac. Although the idea may seem plausible on the surface, when one thinks about it, most of the chemicals that will reduce certain desires will also have other effects such as depression and exhaustion. Randy soldiers are probably better than depressed ones.

The major breakthrough in reducing STDs during the 20th century was the use of antibiotics and condoms. During the Second World War antibiotics became widely available for the first time, and one of their earliest applications was in treating soldiers for STDs along with preventing infection from battle wounds. Post-antibiotics, diseases such as Chlamydia, Syphilis and Gonorrhoea could be, for the first time in history, cured and widely prevented. It is important to note that no other diseases humans suffer from could be controlled as easily as STDs, if people would just act carefully, get checked regularly and rubber up. This should mean with increased education and availability to treatment the number of cases of STDs should be falling; alas, overall cases of STDs are on the rise in the UK.

Viral venereal diseases cannot be treated by antibiotics; you need to have a vaccine or an antiviral drug. The popular account of the rise of HIV in the 80s is well known. A group of homosexual males began exhibiting similar symptoms of chronically depleted immune systems. It was suggested that the disease should be termed Gay Related Immune Disease or GRID for a short while. This soon changed when it became clear that the disease had no affinity to homosexuals. Nevertheless, public prejudices remained and HIV-AIDs was and still is informally called a range of bigoted terms, from the gay plague to anally inserted death. Public perception in certain groups has also begun to question the use of anti-retrovirals as an effective treatment, which any respectable doctor will tell you is plain nuts. Alternative, non-medical treatments for HIV spring from the same mentality as anti-vaccine groups and crackpot new age mysticism.

Currently, virologists do not think that HIV sprang into existence in the 1980s but may have in fact, evolved from Simian immunodeficiency virus (SIV), the ape-form of this virus which was present during as early as the 1930s. Reports from the 1950s of sailors returning from Africa with unusual immune diseases are well known. Arvid Noe was just such a sailor and he was known to be sexually active in Africa. Arvid, his wife and subsequently their daughter, all died of this condition around a decade before the formal discovery of HIV (1983). Another interesting case is that of David Carr, who reportedly never visited Africa and died in 1959. David Carr succumbed to an immune disease that very closely resembled typical HIV-AIDS progression. Yet, testing of his samples, while at first seeming positive for the virus, could not be repeated and hence will remain a mystery.

An event known to biologists as Zoonosis, which is where a microbial disease jumps from one species to another, must have occurred for SIV to form HIV. This is the same process that allowed swine flu to go from infecting pigs to humans. It is not yet known how HIV jumped the species gap, but, again contrary to bigoted ideas, it is unlikely to have been due to bestiality.

Since its discovery, HIV has played a massive role in biological research. Many labs around the world have been working since the late 1980s on a cure and more effective treatments. Mercifully, the actual rate of HIV infection has begun to decline since it was first discovered. This is mainly due to the actions of many groups working to educate and treat people with the disease. While it is currently not possible to cure a person of HIV, excluding the recent bone marrow patient, treatment of the virus has progressed to a great extent in recent years. We are able to greatly reduce the likelihood that a HIV positive mother will pass on the virus to her unborn child, allowing HIV positive mothers to give birth to HIV free children. If you are not impressed with that go back and read that last sentence again and think about the implications. This is something that I, as a biologist, am truly proud of.

It’s all thanks to the current drugs available. The anti-retrovirals in today’s clinics are among the most fascinating drugs ever developed and anyone who takes an interest in biology and drug design would be impressed by their function. Furthermore, the current antiretroviral drugs are so effective at treating people with the virus that the life expectancy of someone with HIV is now only around 5 years off that of any other person alive today. This is the root of the claim that AIDS is no longer a death sentence.

I doubt there will ever be a time when all STDs are “conquered” by science. Diseases change and evolve all the time and while we might make strides in reducing and curtailing some STDs with medical breakthroughs, in some way they are monsters of our own making. Thankfully, they can all be readily screened for and highly effective means of preventing them from being transmitted already exist.

James Gurney

Hello and goodbye, of sorts…

Since I do not think I’ll be able to make any a history of infection videos for a while I’ve decided to start a blog! Stay tuned.