Memoirs of a Defective Brain

Write Up Mode : Activate !

2012-02-03T18:09:00.001Z

Use Thundershock you Fool! Books are weak to Electric !

It's over, and I'm overwhelmed. I've finished my last set of experiments. My feelings upon leaving the lab are difficult to sum up. There is so much more I could've done ! If I'd worked smarter, if I'd planned some experiments better, or if I'd gotten luckier. But the lab work had to stop sometime.
It only hit me how much work I still had ahead of me when I packed away all of the various papers, notes and lab diaries that had accumulated on my desk. It all looked fine, neatly packed into a large duffel bag, until I did my back in trying to lift the damned thing. Distilling a thesis from all of that may take up a lot of my time.
I don't know how this will effect my blogging yet. I reckon I can still find the time to do it, considering how I was still able to do it when spending most of my time in the lab, so in theory I should be able to find time to write/ draw for this blog. But I've never written a PhD thesis before so I don't know for sure. I'm toying with the idea of blogging about the thesis writing process as it happens, but I'll have to wait and see.

The Beetle to Beat TB

2012-01-13T11:11:00.001Z

Over at Infectious Thoughts, Siouxsie Wiles has a video up about her research, which makes a great introduction to a paper that I've wanted to blog about for some time.

The goal of this research was to create a glowing strain of mycobacteria, and looking at this video, one may be fooled into thinking that this research was "simple". This is far from the truth. In fact , the route to getting a bioluminescent strain of mycobacteria was fraught with difficulty.

Getting any bacteria to express genes from other organisms is a difficult process. In nature, bacteria are often subject to attack from foreign genes from viruses. Some bacteria have defenses against this, others simply don't react well at all. many a synthetic biologist has created a "perfect" construct, only to find that it immediately kills all bacteria that express it.

The way in which genes are introduced into bacteria using a plasmid. Plasmids are circular pieces of DNA that can replicate in their host. With the inclusion of special sequences, they can integrate into the genome of the host. different plasmids can do ifferent things. Some of them can replicate a lot in their host, so each bacterium can have lots of plasmids, and therefore lots of copies of a gene. Conversely, you can have plasmids that copy themselves less often. The most extreme form is actually getting the plasmid to integrate within the chromosome, so that there is only one copy, that only replicates when the host cell replicates.

The number of plasmids containing your gene can affect the level to which it is expressed. More plasmids = more gene copies, and therefore more expression of that gene.

And then one needs to think about the gene to be used.

Firstly, whilst this video focuses on the firefly, this video could easily have featured a number of different organisms in its place. In nature, bioluminescence is surprisingly common, and a number of different organisms use different methods to glow. So when setting out to make mycobacteria luminescent, they had three candidates:

Firefly: The beetle that is shown in this video. Firefly bioluminescence is known to require a Luciferase enzyme (called Luc), and a compound known as D-Luciferin. Whilst we know that D-luciferin is needed for bioluminescence, the actual genetic system that creates this compound is not fully understood.

Gaussia Princeps: This tiny marine copepod glows in the dark of the deep sea. It's bioluminescence system requires a compound known as coelentarazine, and is one of the few systems that doesn't require oxygen as a substrate. The copepod itself doesn't make it's own coelentarazine. Instead, it often hunts other marine organisms to obtain it, and it is not known specifically what organisms are producing this compound. So the genes encoding it are not known.

Photorhabdus Luminescens : A nematode/ caterpillar pathogen. When it feeds on a caterpillar, it causes it's carcass to glow to attract more nemotode hosts. The luminescence system for this bacteria is simpler than those found for the eukaryotic organisms, with the genes encoding both the luciferase enzyme, and it's substrate are both known.

These facts will come in useful when thinking about taking these genes out, and actually using them in a practical situation.

One of the problems is the mycobacterium itself. The main purpose of this research was to develop bioluminescent strains of the bacterium Mycobacterium tuberculosis. However, it is probably not a good idea to expose themselves to TB on a daily basis, and moreover, it takes a long time to grow the bacteria. So instead of moving straight into TB, the researchers tested out their bioluminescent constructs in Mycobacterium smegmatis. M. smegmatis is generally non-pathogenic, and grows a lot faster than other strains of Mycobacterium. So it can be more easily used to test out these bioluminescent constructs.

So the author took three plasmids, one which has a high copy number, one with a low copy number, and one which integrates, and then partnered them up with the three different luciferase systems, shown above.

So you'd expect that with more copies of the gene, you would see more light production. What was found was in fact quite different.

In fact the bacteria with just one copy of the luciferase genes glowed better than the bacteria with multiple copies. This same effect was found for the firefly luciferases , and for the bacterial luciferases.

Whilst this initially surprising to me, my synthetic biologist friend simply made some derisive noises along the lines of "well duh". Bioluminescence is an energy intensive reaction. So a bacteria using up a lot of energy for bioluminescence will not have much energy for other important processes, like nutrient acquisition. And so the system feeds back on itself, setting up the paradoxical situation where less really is more.

But this was not the end of it. The amount a certain gene is expressed is also dependant on something known as a promoter. This is a section of gene sequence which controls how much a gene is expressed, by attracting proteins which "open up" the DNA strand, allowing the sequence to be read. They tried a number of different promoters, and found the best one to express the luminescent signal.

Using these techniques, the maximum amount of messenger RNA is made in the cell. But at some level, the decoding of these genes into actual proteins is limited. In order for protein to be made from messenger RNA, each segment of the DNA sequence needs to be partnered up with an amino acids. This decoding wis performed by transfer RNA, which binds to an amino acid, and to a three base pair sequence on the messenger RNA

There are 21 different amino acids which can be used to make up proteins, but 64 different combinations of codons. So some tRNAs that bind to different DNA sequences can bind to the same amino acid.

However, different organisms have different amounts of tRNA. So a firefly cell may have more of one type of tRNA than another, but a bacterial cell may have different number of tRNA.

If you take a gene directly from one and put it into the other, you may find that the protein takes longer to form, and therefore you get less of it.

However, if you take the amino acid sequences for the firefly luciferase, and then translate it into the DNA code according to the most abundant tRNA present in a cell, you can increase the chances of the right tRNA binding to the right area, and thus increase the rate of transcription. This technique is known as "codon optimisation". So the researchers performed this "codon optimisation" and found that it did indeed make the bacteria glow brighter.

So now that they had made sure that their genes worked in Mycobacterium smegmatis, they put them into Mycobacterium tuberculosis and found that they glowed just as brightly. The brightest signal came from the bacteria with the firefly luciferase.

Now that we have this glowing bacteria, we can see where it goes and what it does during an infection, without the need to kill animals at every single time point. And using this technique, the bacteria can show us where they go during infection. This is an unprecedented opportunity to find out, not only how this bacteria causes infection, but also to reveal new treatments to combat it. And all because of one beetle.

Andreu N, Zelmer A, Fletcher T, Elkington PT, Ward TH, Ripoll J, Parish T, Bancroft GJ, Schaible U, Robertson BD, & Wiles S (2010). Optimisation of bioluminescent reporters for use with mycobacteria. PloS one, 5 (5) PMID: 20520722

History of Scarlet Fever: The Fight against Childbed fever, and it's many casualties

2012-01-07T16:47:00.000Z

It was 1790,when Dr Alexander Gordon, a retired naval physician, decided to settle down in the scottish town of Aberdeen . He had had an esteemed career , and a wide experience in treating malady. So when the town was struck by a horrible epidemic, he was the man the local physicians looked to for guidance.
This epidemic of was of a very tragic kind. It affected mothers immediately after giving birth. This childbed fever was usually fatal. The locals referred to it as weeds. Doctors tended to call this "puerperal fever" .This kind of fever has been recorded since the time of Hippocrates, and is referenced in the Ayurveda. But it was never very common. But as the 19th century dawned, this disease became more common. The practice of midwifery was in flux as well. Historically, the main practitioners were women who had deep practical knowledge of their craft, but this was changing. Doctors and surgeons, backed by scholarship and a grounding in anatomy started to practive midwifery. Inventions such as obstetrics forceps revolutionised the field of midwifery. in the mid 1700s, "Lying in" maternity hospitals were established.
for this reason, Alexander Gordon would have been asked to preside over pregnancies as part of his general practice. Most doctors assumed that puerperal fever was a natural consequence of pregnancy, and paid it no mind.
Dr Gordon was different. He did not have any pre-conceived assumptions about this disease. Much in the way as had been set out by Thomas Sydenham, he checked the facts before resorting to theory. He noticed that patients who succumbed to the disease tended to share contacts with eachother, or the midwives that tended to them. Through careful observation, he found that medical practitioners, including himself, were spreading contagion to their patients. In fact, he noted in his publication that the epidemic had not spread to a town outside of Aberdeen specifically because the midwife tending those areas had not become infected. He was the first person to recognise that puerperal fever could be transmitted. And that the main medium of transmission was through doctors.

After making impassioned pleas for change, he was accused as being the cause of the outbreak. He was driven out of Aberdeen, and eventually fell back into Naval service, where he would eventually die from tuberculosis far from home. His work was never fully conveyed to the medical establishment, and it faded into obscurity.
Nearly fifty years later, a doctor from Doncaster by the name of Robert Storr noticed a worrying trend in his patients. In the winter of 1840, there were outbreaks of scarlet fever and erysipelas. And suddenly, he noticed an epidemic of childbed fever. More worryingly, he noticed that if he saw a pregnant woman soon after attending to a sufferer of childbed fever, they too would succumb to the disease. At these instances, he became incredibly anxious. He recognised the one factor that linked all of these patients: himself.
So he began a strict regimen of cleaning himself, and changing his clothes in between patients. So concerned was he that he decided to leave his practice, and take some time out in Wales, with the hope that the fresh air would help rid him of the "poison".
He returned to his practice, and to the treatment of his patients. Within a week of returning, he was called to attend to two pregnancies happening within a day of eachother. And both of those pregnancies resulted in the deaths of the mothers.
The good doctor was distraught. It was his colleague, Dr Thompson who suggested that perhaps Dr Storrs may have re-acquired the "poison" from another of the patients he saw. It was then that Dr Storr recalled that before each outbreak, he had attended one woman, a Mrs Richardson for erysipelas.
Erysipelas is another form of scarlet fever, a fact that had been recognised since the time of Daniel Sennert. In it's most severe form, it can manifest as necrotizing fasciitis. In the case of Mrs Richardson, it had caused massive build up of pus in her leg, making it painful for her to move. Dr Storrs had been alleviating her pain it by draining off the pus. And Dr Storr realised that every time he attended a pregancy after draining off this pus, that pregnancy would lead to a case of fever.
He immediately handed over the treatment of Mrs Richardson to one of his colleagues, and found that his preventative measures began to work. And so he dug deeper. He asked around his medical colleagues, and found that many had similar experiences. One would note how doctors who attended mothers after dissecting corpses would often see those mothers die of childbed fever. And often, this fever would appear linked to cases of Erysipelas. He noted previous work had showed that it was possible to contract erysipelas from puerperal fever, and Storr realised that it could work both ways. He published his observations in the Provincial and Medical Journal. He was the first to realise that the disease of erysipelas, and scarlet fever was also the disease that was the cause of childbed fever. It was well read amongst the physicians of Britain, and soon other physicians came forward with their own stories.
Dr Francis Elkington of Birmingham wrote in support of Dr Storr, having noticed a similar pattern at his local practice in the preceding decade. He had begun to enforce strict hygienic practice when dealing with pregnant women, ensuring that he only wore clean clothes, and always cleaned himself. And as a result, for the past seven years, the numbers of patients who had died of childbed fever fell precipitously. There were only two cases. One happened when he was hurrying home after draining pus from a man by the name of Perry, and he was urgently needed for a woman who was "dangerously ill" and not supposed to be in labour. The second case happened at the house of Perry, where it was likely that he had transmitted the disease to the sufferer.
More physicians in Britain came forward, and soon Dr Storr found himself contacted by an American physician by the name of Oliver Wendell Holmes. He too had been investigating this problem for some time.

During a meeting of the Boston Society for Medical improvement, a peculiar case was discussed. A woman had died of childbed fever, and during the autopsy, the attending physician had sustained a wound. He soon developed Erysipelas, and died. It was said that in the week before he succumbed to this disease. It was said that before he had died, every pregnant woman to whom he had attended developed childbed fever. After fervent discussion, it was determined that more research was needed before they made any decisions as to how to change medical practice. One of the members in attendance, Dr Oliver Wendell Holmes, decided to take up this case. In 1842, he began to scour the literature, to see whether any other doctors had seen anything like this before.
What he found astonished him. He managed to find the first accounts by Dr Gordon published in 1795. As he interrogated the literature, he saw many more cases where physicians, upon suspecting themselves of "poisoning" their patients, enacting hygienic practices to prevent this happening again.
He catalogued a large number of cases, ranging over fifty years, and published his recommendations in the New England Quarterly Journal of Medicine and Surgery.
In England, Dr Storr seized upon this publication as further support for the guidelines he himself had been developing. However, Dr Storr's efforts in promoting these new guidleines ended abruptly with his death in 1847, due to fever.
The New England Quarterly journal never got very much circulation, and Holmes's work only appeared in the final issue. Apart from it's strong support in England, it was not well read. But enough people had read it to find significant disagreement with its findings.
Many physicians in europe and the US maintained that childbed fever could not be contagious, and that it was a separate disease from erysipelas and scarlet fever. In the US, the chief opposition came from two eminent physicians based at the Philadelphia medical school. Dr Hugh Hodges published a provocative article ,describing the "Non-contagiousness of puerperal fever", and was supported by his colleague, Charles Meigs. They suggested that these cases were due to pure chance, or bad luck. They did their utmost to suppress these findings. In fact, Charles Miegs took this evidence very personally,saying that "Doctors, are gentleman. and a gentleman's hands are clean".
On continental Europe, the situation was very much similar. Whilst the USA had Oliver Wendell Holmes to plead it's case, such voices in europe were largely absent. At least, until a physician based in vienna changed this.
Jakob Kolletschska was a professor of forensic pathology. As part of his work, he would routinely perform autopsies on cadavers. He would get his students to help him, pointing out details and abnormalities as they worked. It was during one of these exercises that one of the students accidentally cut him with an unlcean scalpel. The wound became septic, and he died as a result. He was no expert on childbed fever, but his death had a profund effect on his friend at that same institution, Ignaz Semmelweis.
Ignaz Semmelweis had been appointed the head of obstetrics in the Vienna Lying-in hospital, and he was immediately appalled by the numbers of deaths from childbed fever at the hospital. Almost immediately, he set about trying to find a solution to this problem. Semmelweis noted that women who gave birth before reaching hospital tended to not to get this disease.
As the head of obstetrics, he was also aware that every morning, medical students and doctors would perform autopsies on women who had died the previous day. It was these sorts of dissections that Jakob Kolletchska performed on a regular basis, and it was on one of these were he had received his mortal wound.
In 1847, disgusted with his inability to prevent these outbreaks, he took a holiday in Venice. It was while he was in Venice that he recieved word of the death of his friend. When he evenutally got around to reading the autopsy report, he was struck by how similar it was to those of the dead pregnant women whom he had dissected nearly every morning.
He realsied that if it was possible for his friend to have contracted a disease from a cadaver, then it was also possible that he, and his students could transfer this disease to the young mothers in their care. In that same year, he instituted new guidelines to the people workign under him: everyone should wash their hands before they start ont he wards, and before they examined patients.
The results were extraordinary. The numbers of patients contracting this disease fell from 18% to just 3%. But, just as his western counterparts, he faced strong opposition from the medical establishment. Amongst his critics was the "Father of Modern Pathology" Rudolf Virchow, who exerted much influence amongst the medical establishment.
Semmelweis found himself passed over for promotions, and for work as a result of his strong views on handwashing. In the end, he returned to his native Hungary a bitter man. He was appointed to an unpaid position in St Rochus hospital, where he successfully enforced hygiene, and saved lives. He went on to obtain a professorship from the University of Pest and went on to publish his work in 1861, providing crucial statistical grounding to his theories . But he never forgot the insult he was dealt in Vienna.
Whilst some accepted his views, many did not, and they would often recieve a torrent of invective as a result. Semmelweis would publish open letters to his detractors, branding them as "Medical Neros" and "Murderers" in the popular press. He steadily became more unstable, until in 1864, he was committed to an Asylum. He died within weeks, tragically being felled by the very disease he had fought so hard against. But his work lived on afterwards, and his fervour in promoting hygiene was not forgotten.
Many would point to Semmelwies as the founder of hygienic practices in hospitals, but the story is more complex. In fact, the guidelines set out by Semmelweis had been discovered independently by a number of physicians in the west, who were mostly ignorant of each other's work. And the main reason for this was the strong opposition to these findings. The medical establishment didn't want to be told that they were killing their patients, or that their hands were dirty. Many doctors who had seen the effects of hygiene first hand, such as Francis Russell Elkington, implemented changes without telling anyone, and saw their patients improve. But people like Alexander Gordon, Robert Storr, Oliver Wendell Holmes and Ignaz Semmelweis fought hard to get their message out to the rest of the medical establishment. It was not enough for them to be better than their medical companions. We never heard them shrug and say "what's the harm" when they saw their fellow physicians blunder and kill their patients. They went out to change the world for the better, and they paid for it. Most of them ended their lives with their careers in ruin, and lives in tatters. But the lives they saved more than made up for it. They had reached enough people to provoke a groundswell of change. But it was slow and incremental. Whether we remember their names or not, there are people alive today who owe their existence to these men.
Oliver Wendell Holmes was one of the few of them who managed to live long enough to see his work vindicated. Ten years before his death, he met the man whom he held responsible for that. He referred to as "one of the truest benefactors of his race". That man was Louis Pasteur.

References:
Internet:
http://www.donny.co.uk/Doncaster/news/index.php3?ID=1175

Books:
The works of Oliver Wendell Holmes: Medical Essays 1842-1882

Papers

Elkington F (1844). Observations on the Contagiousness of Puerperal Fever, and Its Connection with Erysipelas. Provincial medical & surgical journal, 7 (172), 287-8 PMID: 20793370

Storrs, R. (1842). History of a Puerperal Fever in Doncaster: Illustrated by Ten Cases, with Remarks BMJ, s1-4 (3), 45-51 DOI: 10.1136/bmj.s1-4.3.45

Dunn PM (1998). Dr Alexander Gordon (1752-99) and contagious puerperal fever. Archives of disease in childhood. Fetal and neonatal edition, 78 (3) PMID: 9713041

Storrs, R. (1843). Observations on Puerperal Fever: Containing a Series of Evidence Respecting Its Origin, Causes, and Mode of Propagation BMJ, s1-7 (166), 163-169 DOI: 10.1136/bmj.s1-7.166.163

De Costa CM (2002). "The contagiousness of childbed fever": a short history of puerperal sepsis and its treatment. The Medical journal of Australia, 177 (11-12), 668-71 PMID: 12463995

Adriaanse, A. (2000). Semmelweis: the combat against puerperal fever European Journal of Obstetrics & Gynecology and Reproductive Biology, 90 (2), 153-158 DOI: 10.1016/S0301-2115(00)00264-5

Dunn, P. (2005). Ignac Semmelweis (1818-1865) of Budapest and the prevention of puerperal fever Archives of Disease in Childhood - Fetal and Neonatal Edition, 90 (4) DOI: 10.1136/adc.2004.062901

Colebrook, L. (1956). The Story of Puerperal Fever--1800 to 1950 BMJ, 1 (4961), 247-252 DOI: 10.1136/bmj.1.4961.247

Review of the Year

2011-12-28T22:35:00.000Z

The time of the year has arrived, where we all collectively look back, and go, what the hell was that ?
I remember starting this year, with the absolute certainty that it was going to be terrible. VAT increases, job losses, public service cuts. 2010 was a year of extreme worry.
My Blogger traffic statistics hates 2010 so much that it has been completely expunged from the timeline.

But the traffic statistics also tell another story.
When I started this blog, nearly five years ago, it was purely as a revision aid, to help me set down my thoughts about certain subjects that I was studying. I didn't seek readership, and naturally I didn't get any, Then I started my PhD, and promptly forgot the damn thing existed.
Then in November 2010, I found myself directed to "science of blogging", and once again , enthused, I decided to start a blog. And then I found that Memoirs of a Defective Brain was still here. Everything was just as I left it, even though it had been such a long time. All of the posts that I published, all of the drafts that I intended to publish, but never did. I blew out the cobwebs, tightened up the site design, and started writing posts for research blogging, and for the MolBio carnival.
And something weird happened. People actually started reading. Every spike in my pageview statistics correlated with a spike in dopamine. Of course finding the time to write the kind of blog posts I wanted was (and still is) time consuming. Nevertheless, when the Blogmaster solicited applications for new bloggers to join field of science, I signed up. Probably one of my best decisions ever.
That big spike in my stats in August came from a collaboration of multiple bloggers, where we each discussed the question "Are we doomed ?", and we got some excellent and creative posts about how dangerous viruses, Uncontrolled populations, Incredible Human Stupidity, and the universe is in general trying to kill us. I drew a silly comic where everyone had funny legs.
And since then , I've managed to keep a minimum of about 1,000 page views per month. My proudest achievement has my series on the history of scarlet fever. These have been in the works for a very long time, with many spare moments reading centuries old papers on scarlet fever and streptococci finally paying off. I learned about characters like Johann Weyer, Daniel Sennert and of course Thomas Sydenham, all of whom were interesting in their own right, and each of whom played a role in the History of Scarlet Fever.
And the process of researching and writing for this weblog has helped me innovate my own research, and those of my colleagues. But that's a story I'd like to tell another day, when I (or my colleagues) publish on it.
But it was not all happiness and blog writing. In the wider world, the year was not always so great.

Greece was caught out on it's tax returns, revealing the fragility of the european constitution, and bringing us to the precipice. We still don't know whether the european single market will collapse, and what effect that will have on the UK, but it's out of our hands, since we vacated our seat at the table.
Riots and protests have erupted worldwide. And when these riots turned up on my doorstep, I was surprised, worried and (shamefully) slightly thrilled.
But that same swell of global anger has shaken the foundations of governments worldwide. The Arab spring is the story of the year, with the Tunisian, Egyptian and Libyan revolutions toppling dictators. And every blow was filmed, tweeted and blogged. The power of protest had been demonstrated, and suddenly others worldwide found their voice. If they weren't happy about the way things were, there was something they could do about it. Suddenly financial centres worldwide began to attract occupiers. The idea of popular revolution, remixed and spread throughout the world.
And this is why I have hope for the next year. As hard as times get, humanities propensity for innovation will prevail. The ability to take one idea, re-assess it, improve it and develop and progress is our greatest strength.
And I can show one event that demonstrated this incredible ingenuity, of people taking one idea, and making it their own.

So what do we expect for 2012 ?

More posts on Scarlet Fever's History. You can look forward to learning about great doctors, like Francis Russell Elkington, and Robert Storr.
More Phylomon ! I have been lacking in inspiration lately, but next year I hope to start drawing more bacteria.
And of course, we can expect the giant space god of the Mayans to come down and say "Hey, you guys need a new calendar ? We heard your last one ran out".
And London 2012 will be so bad that the world will end out of sheer embarrassment.

Do you hate slow walkers? So does the Grim Reaper !

2011-12-24T11:43:00.001Z

Researchers in Sydney, Australia were analysing mortality statistics, when they found an intriguing trend. They found that slow walkers tended to have a higher chance of dying early. Could this be a sign of an underlying lack of fitness in slow walkers? Or perhaps that laziness really can kill you ?
None of these explanations were satisfying. But then they realised the one unifying factor in these mortality statistics. Everyone had died. And as you well know, when you die, it is as a result of meeting that fabled entity, The Grim Reaper.

The Grim Reaper, the Harbinger of Souls, Friend to the Friendless, is known to stalk the halls of many a hospital. Despite the fact that this creature is believed to be responsible for 100% of all mortality statistics, it has barely been studied in the scientific literature.

So they did the sensible thing. They set up a study, and enlisted a number of participants, and measured their walking speed. They kept in touch with their participants, checking up on their health and ultimately recorded when they died.

They analysed the relationship between the average walking speed, and the likelihood of encountering the Grim Reaper. And they found that faster walkers do seem to outrun the Grim Reaper. To quote the paper
"Faster speeds are protective against mortality because fast walkers can maintain a safe distance from the Grim Reaper."
"The Grim Reaper prefers to walk at 0.82 m/s (2 miles (about 3 km) per hour), with a maximum estimated speed of 1.36 m/s (3 miles (about 5 km) per hour)"
Older men wishing to outrun the Grim Reaper should maintain walking speeds above these levels. The researchers did say "However, as it is possible that Death’s walking speed varies between work and leisure time,"
In terms of study limitations, they highlighted other problems:
"A further limitation is that we were unable to collect data on the presence of resources that have been reported as enabling people to avoid Death, such as invisibility cloaks, resurrection stones, and elder wands (collectively known as the Deathly Hallows)

They recognise that it is possible to trick, and /or outwit the grim reaper, and to investigate this they propose future work.
"Future research could investigate whether a person’s level of cunning, measured on a suitably developed scale such as the potential CCATBS (the Cunning, Conniving and All-round Tricky Bastard Scale), enables them to walk at slow speeds while still avoiding Death."

So avoid tragedy this Christmas. Walk Faster !

Stanaway FF, Gnjidic D, Blyth FM, Le Couteur DG, Naganathan V, Waite L, Seibel MJ, Handelsman DJ, Sambrook PN, & Cumming RG (2011). How fast does the Grim Reaper walk? Receiver operating characteristics curve analysis in healthy men aged 70 and over. BMJ (Clinical research ed.), 343 PMID: 22174324

When Phylomon fall from the sky

2011-12-19T22:06:00.001Z

The winter winds are blowing. These cold winds whip bacteria up into the atmosphere. These tiny specks of life, unaware of the vast sphere turning beneath them, feel only the cold.

And one particular species of bacterium does something quite special. This bacterium is known as Pseudomonas syringae.

Usually, this unassuming life form lives in plants. It has a number of strategies to attack its plant host, to break apart the cells of a plant to release the delicious nutrients within. Usually, this involves a number of virulence factors, lethal proteins which it injects into the cells. But as winter sets in, this becomes more difficult. The bacterium begins to freeze. But this bacterium still has a trick up it's metaphorical sleeve.

It uses winter as a weapon. As winter sets in, it produces special proteins. These proteins allow ice to form around them, such that they grow out like daggers. These pierce into it's host, ensuring that there will be a nutrient rich bounty waiting for the bacterium when the thaw comes.

But occasionally, a strong wind will blow the bacterium away. And as the bacterium gets higher in the atmosphere, it senses the chill. And, just as it would on a plant, it produces nucleation proteins. Ice crystals begin to form around it. It becomes encased in the heart of a snowflake, and returns to earth.

Hat tip- Scripture of science

Olfactory Reference Syndrome: My attempt at self diagnosis

2011-12-18T16:04:00.000Z

When one is in their first relationship, mistakes are made. There are certain unspoken rules that a novice can accidentally break. Forgetting to hold the door open, laughing at the wrong moment, or believing them when they say "I don't want a Valentines day gift". I had watched many colleagues fall foul of these errors, and vowed to not make these errors with my first girlfriend. I was young, naive and almost certainly scared.
You see, my first girlfriend had several burly, older brothers, which as you may imagine, raised the stakes somewhat.

So the situation is thus. After a day at her place, her mother kindly decided to drop me off at the station so that I could go home. Of course my girlfriend decided to ride along, because it was the decent thing to do.

A perfectly innocent situation, the only risk being the necessarily stilted conversation with the mother. Keep to short sentences. The less words said, the less chance of causing offence.

But then the worst thing that could possibly happen in an enclosed space with both my girlfriend and her mother. But soon, there was something else in the room. It announced it's presence in the most subtle of ways. It was barely audible.
The sound of a zipper being pulled very slowly. As it got louder, it's pitch deepened. Soon, we were regaled with the wet baritone creak of a troubled colon. I didn't, and still don't understand how such a small girl could have created such a noise. I may have been able to keep my composure, if I hadn't had to cope with the humid stench that enveloped the car.
"Did you just fart ?!" I exclaimed.

"No" she responded, with an angelic expression.

"I'm pretty sure...."

" No, I think that was you" With absolute conviction.

At this point , my subconscious began to ring alarm bells. I was about to get into an argument in front of her mother. If I came across as too confrontational, her mother would probably assume that I was a wife beater, and I would have to go to prison, where I would get the stuffing kicked out of me by the aforementioned brothers.*
Just by giving into the juvenile impulse of naming and shaming those who loudly produce gas, I had stumbled into minefield.

What could I do? I could simply keep telling the truth and call her a liar. I could accuse her mother, who was also another person in the car who didn't fart. Only one other option remained.

"oh, err, my mistake" were the words that I probably mumbled. Perhaps this was another one of those unwritten chivalric rules that are alluded to but never mentioned. Maybe all men take responsibility for whatever untoward smells that emanate from their partners. Unless there's a dog present .Then blame the heck out of it**. Dogs don't care.

Or maybe I actually did emit the horrible fart. That would make far more sense*. Perhaps in it's eternal plots against me, my rectum finally devised a way to sneak odours past me without my knowledge. Worst of all, it had learned to throw it's voice. This one incident may have triggered a disorder knonw formally as "Olfactory Reference Syndrome".
This disorder has been recognised in psychiatry under a number of different names since the 1890's, and a recent systematic review set out to examine this as a disease in it's own right.
They set out three diagnostic criteria:

1) The belief that one emits a malodourous smell ("it does not have to be delusional")
2) This belief causes clinically significant distress
3) This is not a manifestation of another disorder, and that this was a unique condition in it's own right.

So they scoured the literature, and found 180 reported examples of this disorder between the years of 1890, to 2009. Of these, only 82 cases were suitable for analysis. Of these, the majority of the victims were male, and the median age of onset was 15.
Often, this disorder would be triggered by a precipitating event, such as the one I described above. So perhaps this psychological trait could explain why I spent the rest of my teenage years doused in aftershave.
On the basis of this trawl through the literature, the authors suggest that this should be recognised as it's own disorder. However, It should be noted that a large proportion of the cases excluded from this study were done so because the delusional odour manifested as a part of different psychiatric disease.
But here is the thing. Whilst I may have gotten slightly paranoid over this event, it never got to the point where it caused significant distress. The "significant cause of distress" in my life dumped me soon after this event. Whilst I woried about it, it never spilled over into the kind of pathology seen in real sufferers from this disease. People who genuinely smell odours that are not there, people who end up obseesively trying to manage odours that aren't present. In some cases, it ended up getting to the point where their doctors had to prescribe medical treatments to get them to stop.
My technique of occasionally dousing myself in aftershave before meeting people seems tame by comparison. Like many psychological traits, this syndrome can manifest at many levels of severity, and only a relatively small portion of people express it severely enough to actually qualify as sufferers. My case was easy enough to get over. I now have a huge collection of aftershave that I no longer use. Although people still keep giving them to me at birthdays, Christmas, Easter, Thanksgivng, and Ohmygodgetyourarmpitoutofmypostcode day.

* this was what passed for logical thinking when I was a teenager.

** For a long time I suspected this was the real reason rich girls carry dogs around in handbags.

Begum M, & McKenna PJ (2011). Olfactory reference syndrome: a systematic review of the world literature. Psychological medicine, 41 (3), 453-61 PMID: 20529415

History of Scarlet Fever : Dancing fever, Civil War and a Revolutionary Scientist

2011-11-19T11:57:00.003Z

Once upon a time, there was a wicked and vain queen with a strong desire to murder her stepdaughter. However, through a convoluted series of events involving a huntsman, seven dwarves and a handsome prince, the stepdaughter survived. In fact she ended up engaged to the handsome prince. As a wedding present to his new bride, the prince invited the queen to the wedding. A show of forgiveness? Not exactly.
As part of the nights entertainment, the queen is forced to wear a set of red hot iron shoes and dance for the amusement of all the guests. Until she drops dead. The moral of this story?

Don't f*ck with Snow White.

Whilst this may seem like a cruel and unusual punishment for us, dancing yourself to death was a genuine fear for people when the Snow White legend came into being.
A medieval medic, known as Felix Platerus records a curious case involving a young lady. She appeared to have a supernatural compulsion that forced her to dance. Guards had to attend to her for a whole month to prevet her hurting herself, or others. She danced until her feet were rubbed raw, and she could no longer stand. And then when she could stand, she started dancing again. A few of the writers of the time make references to Arabic descriptions of "Jumping limbs" and palsy, and a number of writers tended to notice the convulsiveness that characterised these dances.

In northern europe, it was believed to be caused by some form of demonic possession, and sufferers had to pray to St Vitus (the patron saint of dancers) to be relieved of this disease. In Italy and Greece, it was believed that the cause of the disease was from the bite of a wolf spider. The remedy for this disorder was a frenzied dance which eventually became known as a tarantella.

It was not only these nations that took up dancing as the cure for this disease. In parts of Germany, magistrates employed people to play music for these people, and for others to act as dancing partners. This was to allow them to "dance out" their disease.
Choruses of sufferers roamed the streets. Musicians followed them, attempting to soothe their disease by providing rhythm. The greatest challenge in managing this chorus was ensuring the safety of the people who ended up collapsing from exhaustion.

In Strasbourg 1518, an outbreak of this fever prompted the council to set up a guildhall especially for the dancers, and paid people to dance with them, and others to play music for them. Yet still, many danced themselves to exhaustion, and death. Eventually, the Strasbourg council realised this treatment was not working. Still unaware of the cause of the disease, and wanting to prevent contagion, the city banned all dancing. The sufferers who still danced in spite of the ban were sent on a pilgrimage to the shrine of St Vitus. Once they arrived they received holy oil, and red shoes.
These choruses of dances lead to a particular name being ascribed to the disorder- a Chorea. The literature documenting this disease is so littered with allusion and innuendo that it is difficult to get to the truth of the source of this illness.

And into this quagmire strolls the hero of this particular story. His name was Thomas Sydenham. He was a physician of the practical sort, whose personality and career was wrought in the events of the English civil war.

The English Civil War can be said to have begun with one man. When King Charles came to the throne, he had high ambitions. He wanted to finish his father's work, to bring unity between Scotland, England and Ireland. Furthermore, he wanted to enter the brutal "Thirty Years" war that had been raging on the continent.
But what was more controversial was how he dealt with parliament. At the time, parliaments control was far less than it was today. It collected taxes, and controlled how they were spent. If the king wanted to use any of that money, he needed to consult with parliament. Charles however, was believed in the king's "Divine Right" to rule over his subjects, and that he should answer to no-one but God himself. Needless to say, there was some friction between the King and his parliament.

One example is when Charles demanded funding for an expensive military campaign on the continent. Parliament, initially supportive of this course of action, questioned him over putting one of his friends in command, instead of more competent individuals. Their fears were confirmed when the war ended in an expensive defeat. When parliament attempted to bring charges against the man responsible, Charles dissolved parliament.
Such exchanges began to characterise the King's rocky relationship with his kingdom. Charles needed parliament to fund him, but in return they would want a say in how the money was spent. So the king stopped convening parliament, and attempted to rule the kingdom as an autocracy. He levied new ( and illegal ) taxes upon the populace, as a replacement for the parliamentary purse. He instilled a new religious doctrine, and began to persecute those who did not adhere to it. For those in religious minorities, this was a worrying chain of events. Puritans, such as Thomas Hooker, sick of the religious persecution, emigrated to America.
The Scot's also did not take these changes lightly. Soon, they were in open rebellion, and the King didn't have the money to fight them. So after eleven years of "personal rule" , Charles was forced to convene parliament again, to secure more funds.
Various members of parliament saw this as an opportunity to bring their king under control, and introduce more reforms. It did not turn out that way. Predictably, this resulted in another quarrel, and in less than a month, parliament was once again dissolved.
The king went to war anyway with what little funds he could muster. The ensuing fiasco ended with Scotland in control of the North of England. The Scots, magnanimous in victory, promised they wouldn't burn all of the cities in their possession so long as Charles paid them a ransom.
The King couldn't just let the north burn. He needed to reconvene parliament . In return for the money, reforms were enacted that aimed to end the king's autocratic habit. But Charles would not crack so easily.
By the time Thomas Sydenham began his studies in Oxford, events had come to a head. In January 1642 King Charles had marched with 400 men to parliament with the intention of arresting 5 of it's members, but without success.
Across the country, towns and constituencies began declaring fealty to either king or parliament. War was brewing. Parliament began recruiting an army to do the unthinkable. To fight against their own king.
In the early stages of the war, Sydenham's mother was killed when Royalists raided their home. This act which drew the whole family deeper into the conflict.
Sydenham left Oxford, and joined his family to declare loyalty to parliament. Their exploits during the war lead them to be known as"The Fighting Sydenhams".

Thomas's older brother, Francis Sydenham became a legend in the Parliamentarian army. When attacking the seemingly impregnable town of Corfe, it was Francis who oversaw the construction of tank, which was used to great effect to assail the city.
At one point, Francis pretended to defect to the Royalist side against his own family. In doing so, he tricked Royalist forces into entering a devastating ambush in Poole. And during that battle, by chance he encountered the man responsible for the death of his mother, and killed him on the spot*.

Thomas's role in the war is largely overshadowed by those of his brothers and his father. It is known that he was wounded in a cavalry charge at the battle of Weymouth as the war was drawing to a close. By the time the royalists had surrendered and the king executed. Two of his brothers, including Francis, were dead. It was a new England, with Oliver Cromwell and parliament in charge.
Thomas Sydenham returned to Oxford to take up his studies once more, and found it a much different place. It had been one of the last royalist strongholds to fall, and Parliamentary forces aimed to keep it under strict control. Parliament had put "visitors" in place, who enforced parliament's political will on campus. They expelled anyone who spoke out against the new government.

Thomas, being a leading member of the revolution, thrived in this environment. Parliament were eager to bestow some commendation upon him for his family's role in the war. As a result, ended up with a doctorate within his first year of study. In addition to this, he may also have played a role in helping Cromwells "visitors" in expelling professors on the basis of their royalist leanings. This removal of old academics aided the careers of younger academics such as John Locke and Robert Boyle, both of whom were friends of Sydenham.

Nevertheless, the army was not yet done with Sydenham. Whilst Cromwell had successfully won the civil war, winning the peace was a different matter. After returning from a brutal and bloody campaign in Northern Ireland, Cromwell turned his eyes north. The Scottish parliament were jockeying for more power in the new order, and recruited the heir to the throne, Prince Charles II to force the issue. In 1651, Cromwell answered with an army of seasoned veterans. Once again, Thomas Sydenham found himself at war. He was put in charge of his own battalion, where he used his medical knowledge to fortify his troops against the northern frosts. But this didn't stop him from being left for dead on a battlefield and nearly shot at point blank range by a drunken trooper from his own side. When Scotland was defeated, Thomas left the army, never to return.

He devoted the rest of his life to the study and the application of medicine, and managed to revolutionise the way it was practised in England. At the time, there were many explanations of diseases, and often doctors would prescribe treatments accordingly. The vast increase in anatomical knowledge lead physicians to prescribe bleeding to balance the "humours" that allegedly controlled the body. Various beliefs on matter, and findings in chemistry lead to mercury being used as a purgative. The best "treatment" for a convulsive jerking disorder at the time was to "dance" the demons out.

When the founder of the British museum, Hans Sloane applied to be a student of Sydenham, he presented the physician with a letter of introduction . Sydenham glanced at the letter. It indicated that Sloane was "a ripe scholar, a good botanist, a skillful anatomist".
"This is all very fine," Sydenham cried "but it won't do! Anatomy ? botany! Nonsense! Sir, I know an old woman in Covent Garden who understands botany better, and as for anatomy, my butcher can dissect a joint fully as well. No, young man, all this is stuff; you must go to the bedside; it is there alone you can learn disease."

He recognised that many of the findings of anatomy and science were very much in their infancy. The application of their principles when they were so poorly understood was foolhardy. He staunchly believed that evidence was the guiding factor at the bedside.

"It is my nature, to think where others read; to ask less whether the world agrees with me than whether I agree with the truth" he says in one of his works. He flatly states that to speculate on the causes of diseases was a "difficult and perhaps inexplicable affair; and I choose to keep my hands clear of it".

He was one of the few men of the day who recognised that they simply didn't have the tools to speculate on the causes of disease, and that the bedside was a far better teacher than the library.
What Sydenham frequently found was that the application of unproven theories to the treatment of patients did more harm than good, and that often the best thing to do was to let nature take its course.

Sydenham had very little patience for nonsense. So one wonders what he thought when he first heard of the dancing fever. When he first encountered a patient, He did not speculate on whether it was caused by demonic possession, or by a spider bite. He focused on collecting as much information as possible about the disease, and then letting the evidence speak for itself. He described the patients as exhibiting convulsive movements out of their control,** . Instead of prescribing dancing, or prayer, he simply let the disease run its course, and found that patients would eventually get better without interference. The deaths attributed to this disease were probably caused by the forcing of sufferers to "dance out" their disease. Whilst he did not know it at the time, this dancing disease was related to another disease he studied, the disease that is the subject of this series.

It was Thomas Sydenham who gave scarlet fever it's name***. His initial studies on epidemiology in 1666 are where he first describes the disease, although the actual name “Scarlet Fever” only appears in the 1683 edition. . He noted the seasonality of this disease, and made key observations on it's disease course, and that the treatments of the time were at best ineffective.
Unfortunately, his description of the fever leaves out many of the essential details that were catalogued by Sennert. Sydenham's failure to recognise the more severe forms of this disease (such as the dropsy and arthritis) meant that subsequent physicians often confused it with measles. Such was Sydenham's repute that his word was deemed to be the last one on this issue for over a century.

Nevertheless, his work was revolutionary. The Dancing fever would eventually be named after him, and called Sydenham's Chorea, and the wide regard of his work raised awareness about Scarlet Fever.
Unbeknownst to him, the two diseases are linked. Previously, I talked about how Sennert was amongst the first to recognize that scarlet fever can trigger other diseases, such as "dropsy" and rheumatism.
Today we know that these occur because the bacteria that causes scarlet fever, Streptococcus pyogenes, often uses a variety techniques to hoodwink the immune system. In some cases it can turn the immune system against the rest of the body. These immune reactions are what cause these "disease sequels".

In the case of Sydenham's chorea, the immune system has a bad reaction with the nervous system, causing damage. This manifests itself as the juddering dancing motions characteristic of the disease. It usually resolves of its own accord after the underlying bacterial disease is cleared. So Sydenhams basic treatment of "Wait and See", or even the religious method of "Wait and Pray" would have worked far better than other treatments available at the time.

But what Sydenham did for medicine was not limited to his descriptions of diseases. Indeed, in many of his writings he often proclaims his ignorance on many subjects. It was the way he practiced medicine that secured his place in history. His re-introduction of Hippocratic methods of evidence gathering were the key to his success. After his death, the following was written of the great practitioner;

"The great merit of Sydenham, was to proclaim the great truth that science was, and always must be incomplete; and that danger lurks in the natural tendency to act upon it as if it were complete. A practical man has to be guided not only by positive knowledge, but by that which is imperfectly known. He must listen to the hints of nature, as well as to her clear utterances. to combine them may be difficult; but the difficulty is solved in minor matters by the faculty called common sense; in greater affairs by the synthetic power of Genius " ***

Footnotes

* In one account , it was said to be Thomas himself who avenged his mother, but sources that are more reliable indicate that it was actually Francis.
** There seems to be a bit of controversy over the actual causes of the medieval dancing disease. Whilst the diagnosis of Sydenham's Chorea may make sense in the context of the devastating streptococcal outbreaks pushing their way through Germany at the time (as documented by Weyer and Sennert), it does not explain everything.
The medieval descriptions of the sufferers of Chorea differ much from Sydenhams own account. They talk of sufferers leaping and so forth. It is the impreciseness of language that makes it hard to definitively describe the disease. It appears that only arabic accounts agree with Sydenham's description, but I have not been able to source the relevant documents to back this up, and even if I did, I can't read arabic.
It is also likely that hysteria may have played a role, especially where people were employed to dance with these victims. In fact, the dancing bans in Strasbourg likely helped to quell the spread of this hysteria.
There are also theories that a rye fungus outbreak spread hallucinogenic substances on foodstuffs, although nothing in the accounts I read indicates that these dancers were actually hallucinating.
The truth is that there is no truly satisfactory explanation for this disease. Sydenham's explanation was good enough for those who lived contemporaneously with the disease, so I decided that it was good enough for me.

***Samuel Pepys is probably the first person recorded to use the term "scarlet fever" to describe a disease, it is unlikely to refer to the disease we know today. It may have been used interchangeably with measles, and other diseases that produced a red rash. It should also be noted that colour based adjectives were often imbued with some form of emotion, with "scarlet" and "black" being not only descriptive, but emotional terms. When researching these articles, I was struck by how almost every disease was described as a "black plague", including those which exhibited streptococcal symptoms. But in some cases, the writers may have well have said "terrible plague" or "scary plague". This use of language makes investigating diseases in the past a very confusing affair to the novice.

*** I have scoured the internet for the source of this quote, and came up with zip. Any help with this would be appreciated.

References

Google Books

"A History of Madness in Sixteenth-Century Germany" By H. C. Erik Midelfort

"Anatomy of Melancholy," by Robert Burton

"The continuum companion to Locke", by Sami-Juhani Savonius-Wroth, Paul Schuurman, Jonathan Walmsley

Dr Thomas Sydenham- by Unknown.

Journals

Rolleston, J. (1928). THE HISTORY OF SCARLET FEVER BMJ, 2 (3542), 926-929 DOI: 10.1136/bmj.2.3542.926

Fischer WJ (1913). THOMAS SYDENHAM, THE ENGLISH HIPPOCRATES: (1624-1689). Canadian Medical Association journal, 3 (11), 931-46 PMID: 20310434

Microbial Phylomon: It came from beneath the Petri Dish !

2011-10-31T08:22:00.002Z

A special halloween edition of microbial phylomon.

First up, the Brain Eating Bug

The frankenstein bug !

And finally the beast with five genomes !

A special thanks goes to BruceDSTaylor on reddit for their suggetsions.
I haven't been posting much recently, although I am still working on a couple of posts and phylomon, my time has been taken up with writing papers and getting my stuff sorted out for PhD. So the posting is going to suffer for a fair bit.

Have a spooky halloween ! Whatever you are -ah-ah-ah

History of Scarlet Fever : Werewolves, Sennert and Scarlet Fever

2011-10-05T10:19:00.002+01:00

I have previously talked about Johann Weyer, a prominent medic with an interest in witchcraft and magic. In the early renaissance, superstition still ruled, and there were a number of scholars at the time who maintained an interest in the occult. Weyer was one of these. I've already talked about his work with respect to witchcraft, but I did not however talk about his work on Lycanthropy. That is, Werewolves.
The werewolf legend specifically refers to people who can turn into wolves on the full moon, or simply at will. These people were the undead, cursed individuals who roamed the earth to do the devil's work.
The Lycanthropic* legends can be found in various cultures and iterations, but it boils down to one thing: an individual who can, at will, turn into an animal.

During the witch hysteria of the middle ages, people in general were on high alert for supernatural activity of any sort. As well as women bieng convicted as witches, there were men who were tried as werewolves.
Weyer met with a number of them, including a man in Padua who could not be convinced that he wasn't a werewolf (Despite the threat of being burned alive). another man, a spaniard, held the belief that he could turn into a bear. Weyer's conclusion was that these people, like the witches he had previously encountered, were deluded, and should be put into asylums, as opposed to being executed.
But Weyer didn't have the last word on this, and there were many who speculated on the source of this peculiar malady.
Ten years after Weyer made his observations on a scarlet fever outbreak, Daniel Sennert was born in the city of Breslau, at that time controlled by the Hapsburg's.
Sennert wrote extensively on topics ranging from medicine to science. It has been evinced by some that he came up with "corpuscular theory", which is the theory that all matter can be divided into small particles, which in turn could be subdivided into smaller ones and allow materials to change form. But at the same time, he also seemed to believe in the competing theory, atomism, in which the world is made of indivisible spheres of varying sizes that cannot be broken down.
Sennert, like Weyer , grew up in a superstitious atmosphere. Despite Weyer's many travails, werewolf and witch hysteria still permeated the public consciousness.
In one of Sennert's books , he writes of a mythical creature known as the Baslisk.
A basilisk is a strange creature that is born from athe egg of a rooster, or a hens egg hatched under a toad, depending on who you ask. It also looks different depending on who you decide is your source. However, what is shared in all of it's legends is how it kills ; a lethal gaze.
Sennert writes of an incident in Warsaw in 1587, where a basilisk was believed to be lurking in a cellar. Two children and their nurse went into this cellar, and did not leave alive. The local inhabitants came up with an interesting solution to this situation.
They took a condemned criminal, and cut him a deal. He could go down into the cellar and face the basilisk, and should he survive, his sentence would be commuted.
He accepted, and was kitted out in protective coveralls, and a suit of mirrors, to ensure the basilisk's fatal gaze would be focused on it's own reflection, thus causing it to kill itself. The man descended into the cellar, and when he came out, he announced that the basilisk had been killed. He described a strange creature that had the "figure of a fowl, eyes and extra feet like a toad and highly coloured with spots".

Behold, the most terrifying Basilisk !

This account shows the fundamental differences between Sennert and Weyer, that become all the more startling when you look more closely. Sennert attended the University of ~~Hittenberg~~ Wittenberg where he studied chemistry and medicine. But as he became more well regarded, he showed more credulity to the practice of magic. In contrast, Weyer was trained by a magician in the occult in his early years, and developed into a more sceptical physician.
Whilst Weyer's assessment of werewolves and witches was that they were mentally ill, Sennert took a different approach. Whilst he acknowledged in some cases that "natural Lycanthropy" can occur, which matches Weyer, he also believed in "Diabolical Lycanthropy" which was caused by the Devil.
This was not to say that Sennert did not make any useful contributions to the science.
As a practical chemist, he performed many experiments which helped him formulate his opinions on corpuscularianism.
Sennert also read a lot and widely about science, philosophy and alchemy, a fact that is reflected in his many writings. it is because of this that he was familiar with the work of Giovanni Fillippo Ingrassia. So when there was an disease outbreak in Wittenberg, he recognised the characteristic "Rubiolae" described by the eminent Sicilian.
Sennert not only diagnosed these patients, but took it upon himself to study them as the disease developed.
He noticed that when scarlet fever subsides, the extensive skin rashes damage the skin and cause it to flake off. This characteristic "desquamation" had never been recorded before. But this was not all he found.
Recovering patients would also experience swelling in their joints and arthritis. He believed that there was a connection between these symptoms and the preceding scarlet fever. That these were "sequels" to scarlet fever.
This finding would still be controversial for nearly two hundred years afterwards. Part fo the reason for this is that these sequels did not necessarily occur immediately after the disease.
It is because of this that Sennert is not remembered for his belief in basilisks, or for his ideas on werewolves. He is remembered for what he got right about scarlet fever; not what he got wrong about the supernatural.

*despite the greek language roots, the word "Lycanthropy" can be used generally to describe any form of animal/man hybrid.

References:
Books (accessible via Google Books)
Chapter 7 , History of Magic and Experimental Science Part 12 by Lynn Thorndike, reprint 2003

Anatomy of Melancholy Part 1 by Robert Burton 2002 reprint

Journals

Michael, E. (1997). Daniel Sennert On Matter and Form: At the Juncture of the Old and the New1 Early Science and Medicine, 2 (3), 272-299 DOI: 10.1163/157338297X00159

Rolleston, J. (1928). THE HISTORY OF SCARLET FEVER BMJ, 2 (3542), 926-929 DOI: 10.1136/bmj.2.3542.926

In which I attempt to review "The Psychopath Test"

2011-09-11T15:17:00.000+01:00

When I first saw him, he was in the queue to see The Infinite Monkey Cage (Prof Brian Cox's Radio show) at the Cheltenham science festival. I noticed him immediately, in the queue, carrying a laptop under his arm.
In the cluttered teenage bedroom that is my brain, I tried to work out where I recognised him from. He wasn't my year 7 biology teacher, although they look strangely similar. Then it clicked. After 10 whole seconds of staring at him, and him smiling back.
But at this point it was irrelevant. If I stared for a second longer, I'm pretty sure I would look like a gormless psychopath. I didn't want to offend one of my favourite scientists, so I peeled off quickly, trying not to be more of an embarrassment than I already was.
I spent all of 5 minutes wondering what I would have said to him, and cursing myself for not being quick or bold enough to start a conversation. But at ChelSci there really isn't much time to dwell on things like that, and soon I was off to the next talk. I probably wouldn't get another chance to meet him, so it was best not to dwell.
However, after one of the lectures I decided to get some reading material for the 3 hour journey back to London from Cheltenham. Luckily, they had opened up a Waterstones at the science festival, so I could go in and get a copy of a book that I'd heard a lot of good publicity about.
And right by the entrance, I saw the man I had accidentally glared at earlier.

PZ myers was in waterstones, peering at a shelf of books. For those of you who don't know, PZ is probably the best blogger still remaining at scienceblogs.com and an outspoken proponent for atheism.
And now was my chance to have a conversation with him, a golden opportunity, although probably not as good as when he was bored waiting in a queue. But still, I'll take what I could. I wouldn't squander this opportunity like I had with Richard Dawkins.
When I was a lowly undergraduate in my first year of study, there was an interesting event happening at the museum adjacent to my campus. There was a discussion over the full extent of evolution in our daily lives, which I thought would be fascinating. I tried to get my friends to go, but they didn't really go for it.
At the end of the discussion, I bumped into Richard Dawkins whilst he was waiting for his cab. He had been one of the speakers, and had talked a fair bit about stuff from his book, the extended phenotype. However, at this point in time, I had little or no idea who Sir Richard Dawkins was. All I knew was that one of his books was listed on the syllabus (the selfish gene) and that he was an inspiring speaker. I knew he was an important person, but i didn't quite grasp why. It was because of this that I had a conversation with Sir Richard Dawkins about.... the english weather.
when I got back to halls, and mentioned this, I was met with uproar and hand wringing. firstly, how come I didn't tell them that Richard Dawkins was part of this talk, and secondly how I wasted an opportunity to talk to him.
But this time would be oh so different. and it was, I knew exactly who PZ myers was, and I'm sure I would have something interesting to talk with him about. Inside my brain, a little homunculus was putting together all of the folders marked "pharyngula" together with an aim to put everything together for a conversation.
"Hi are you PZ myers? "
"yes"
"I read your blog"
"oh, and who are you?" he said raising an inquisitive eyebrow. The tiny homunculus in my brain frantically attempts to find intelligent responses, but defaulted to the truth
"[--insert name here--]" there was a silence "I am a PhD student studying infection" i didn't know what that information contributed, except another short pause, which I dutifully filled with more words. The homunculus pressed the stream of consciousness emergency button, which is always a tricky manoeuvre.
"I'm not sure the right way to introduce myself, or whether i should define myself by my qualifications"
"oh, don't worry about that"
Great, now the initial awkwardness is out the way , conversation can start. The homunculus proudly opens the "pharyngula" folder of conversation topics. Funny, I thought there would be more stuff in here. Ah, PZ is an american. My prejudices tell me that americans don't often leave america. let's go with that.
"oh, I didn't expect to see you in england"
"Oh well, I've been doing talks in glasgow and other places. I'm just taking some time off and enjoying the sites"
My internal homunculus realises that almost all of the pharyngula facts strewn over then floor of the office of my brain. "Stall for time whilst I get these together," it would have told me if it existed.
"Oh, did you catch the Infinite monkey Cage" I said, wryly accessing my short term memory.
"Oh yes" PZ replied "a little too much physics for my liking, not enough biology"
"Well" I improvised " Biology is the language of love "
Jesus, where did I get that corny line from ? Was I coming on to him? I definitely didn't want to come on to him. I didn't want to frighten the old gent.
"oh" PZ responded " I never thought about it like that"
"oh, and it's responsible for hate and other emotions "
Well on the bright side he definitely knew I wasn't coming on to him. On the downside I was failing to conceal my lunacy.
"Oh, well I'd better get back"
"Oh yes, of course" Thank god. Who knows what bullshit I'd've said next.
"Nice meeting you" he said
"you too, and thank you for blogging"
To which he smiled and gave a polite reply, before taking his place in front of the books. Perhaps I should have opened with that, but never mind, the moment had passed.
I walked off glad the pressure of the conversation was over. I was about to walk out, but then I remembered that I still needed to get that book. It was the psychopath test by Jon Ronson. He was speaking later in the conference, and I had read a bit of the publicity spiel for it, and it seemed like it would be a good read. I turned back and saw that it was on the very same shelf PZ was looking at. Having already said my goodbyes , I didn't want to invading his personal space once again, or worse get into another painful conversation.
I could have waited until he left. But wouldn't that be even more suspicious, wringing my hands and glaring just on the periphery of his vision ? I'd probably get arrested.
Instead I decided to go past and grab the book as quickly as I could hopefully without him noticing. In my mind I was a book grabbing ninja, but in reality I was the twat who barged past PZ myers to get a book. My escape may not have been graceful, or cunning but it was hasty.

And this was how I ended up with a copy of The Psychopath Test by Jon Ronson. In retrospect, my odd behaviour around PZ myers left me in the perfect state of mind to read this book, for it was about how craziness, ranging form the mild to the severe, affects each of us and how it affects society on a larger scale.
It was one of those books that I simply could not put down. It begins with a simple story of the author investigating the erratic behaviour of one individual, and how that behaviour affected a number of different people in interesting ways. From there, he diligently investigates people with personality disorders, and how the treatment and diagnoses of these individuals have affected us.
Through his research, he met an individual who faked madness to avoid prison, and ended up indefinitely detained in broadmoor. Funnily enough, most of his doctors knew he faked psychosis, but determined that this was a symptom of psychopathy. And through this story we enter the strange kafkaesque world of the madness industry.
It was at this point in reading the book on the way from London to cheltenham that I finally give in. You see, a large part of the time I spent reading this book on the train, a loud mob of cricket fans have sat next to me in the carriage. In particular, a very inebriated individual whom I would come to know as "Nobby" sat down next to me, with a half pint still in his hand. From his red features and slurred speech, I presumed that this was not his first one. The train guard had noticed that Nobby was carrying a beer on public transport, but wisely didn't harass him about it when he wasn't making a fuss. In fact, none of these events were enough to tear me away from the book. The fascinating story of Emmanuel "toto" constant, a Haitian mass murderer inexplicably living with his mother in a New York suburb verged on the unbelievable.
However, for around half an hour, "Nobby" had been loudly announcing to the train carriage that he needed to go take a piss. He went to the train loos, and found that all of them were locked. Still I read the book.
Nobby then started complaining that he'd piss himself, and he needed a bottle. It was when one of his friends suggested that he should take this opportunity to"top up his pint" that I cracked up. And that was how I got into a conversation with "Nobby".
admittedly, all I could really get out of him was how incredibly desperate he was for the loo, and how he couldn't believe that not only both the loos were occupied, but that they were occupied for so long. He was right not to, so it transpired. The train guard eventually noted the mans distress, and unlocked the lavatories. The were empty all of this time.
Apparently, the policy of british rail is to lock all lavatories on some local journeys to stop vandals from destroying them. And that was why Nobby nearly pissed himself. And it was why, a notably more relieved nobby, was still furious with the train guard. The train guard to his credit took the verbal abuse with good humour, and did his best to not inflame the situation.
Eventually nobby cools down a bit, and notices that I'm reading a book. I say that it's about madness. He looks straight at where I presume he thought my face was, winked blearily and said "well, everyones a bit mad. I'm mad. I'm definitely mad, but I guess you've noticed that. Everyone's a bit mad"
Which is funnily enough, one of the conclusions you can take from the psychopath test. In the book, the author, Jon Ronson learns the art of diagnosing psychopaths. And he meets a number of characters, from a ruthless corporate executive, to an overly rude concierge, each of whom are described on the psychopathic spectrum. He demonstrates the old adage that a hammer wielder sees a world made of nails. Once armed with the "psychopath test" he sees madness everywhere. And so will you.

The point is that when you have these tests, one tends to extrapolate from the most extreme bits of behaviour. Nobby was not a lunatic, despite behaving like one. In this extreme situation, where he was both too drunk to stand, and suffering from a strained bladder, and surrounded by equally drunk (if more restrained) friends, he behaved like an impulsive mad man. But I am only observing him at his most extreme edge. I have no idea what he's like the rest of the time, so I can't make a solid diagnosis based on this.

Having finished this book , I went into a joint session on the human mind, with Richard Wiseman and Jon Ronson. Anyway, it was nearing the end of the question and answer session that a distressed lady came up to the microphone. She had not read the book, but had read in various reviews that it took a light hearted and comical view of mental disorders. Having suffered from mental disorders herself, she was not happy with what she saw as the trivialisation of these diseases.
It was for this reason I hung out at waterstones afterwards, so that if she turned up to attack him, I'd at least get a good view.
Whilst I was waiting for this event to occur (It didn't) I thought a bit more about her statement. Evidently, it was never the authors intention to trivialise mental disease. He references cases of people who genuinely suffered terribly from psychiatric disorders, and how doctors struggled to find ways to "cure" them. But this book isn't just about psychopaths, and those who we regard as mad. It is how we respond to madness in the modern era, and how this response affects us and our society as a whole.

What I'm saying is that I highly recommend that people read this book. In fact I would recommend you read it as I did, fumbling through a conversation with a personal idol, and then whilst absently consoling a drunken yob whose only real desire was a working lavatory.

Even More Microbial Phylomon !

2011-09-04T19:42:00.000+01:00

Even more Microbial Phylomon as requested by you the readers!

Microbial Phylomon and friends

2011-08-30T16:11:00.000+01:00

I'm currently running low on ideas for what bacteria/fungi/protists/viruses/archaea I should convert to phylomon next. If you have any suggestions, please leave them in the comments.

History of Scarlet Fever: Witches, The Occult and The Renaissance

2011-08-24T11:18:00.001+01:00

In the last installment, we looked back to the time of Hippocrates, and his description of a streptococcal disease in 430 BCE. We continue with the story some two thousand years later.
It has been a turbulent era, with empires falling, fiefdoms rising and a decline of scientific thought in the western world. The era described by Petrarch as the "Dark Ages" was coming to an end, with sparks of the enlightenment appearing over europe. The fruits of Arabic golden age philosophers such as Avicenna, al-Razi were reaching various libraries and scholars.
It was the time of Heinrich Cornelius Agrippa, who was famous for his works on magic. It was these that often attracted ire from the religious orthodoxy that dominated Europe. He is an intriguing historical figure, but not the focus of this piece. the focus is on his student, Johann Weyer. Regrettably, Agrippa died before Weyer could finish his training with him. At a loss, Weyer ended up attending medical school in France. It was these experiences which moulded Weyer into an expert in both medicine, and magic.
It was these two skills which became useful to him when he encountered the "Malleus Maleficarum". For those of you not up to date on hysteria inducing books of the 15th century, let me explain. This book consisted of the "evidence" that witchcraft existed, the forms it took, and advice on how to catch them. Endorsed by the church, copies of this book spread throughout europe, and fuelled the hysteria that lead to Witch hunts.

Johann Weyer :Extra points if you can spot the optical illusion

Weyer however, debunked the Malleus Maleficarum in his own book "De praestigiis daemonum".
In it, he presented evidence that these women were afflicted with mental issues, and should handled by physicians, not law courts and angry mobs.
Whilst he never doubted the existence of supernatural entities such as demons and angels, he was sceptical of the degree to which these beings interracted in human affairs. As he got older, he moved away from magic, and concentrated more on the study of medicine.
In the winter of 1563, Weyer recorded the outbreak in lower germany referred to as "The Great Plague" . In his account , he states that this disease had spread to various cities in Europe, such as Danzig, Vienna, Cologne and even London.

In the region of the lower rhine, A disease appeared that caused swelling of glands in the throat, which was associated with a characteristic rash. This pestilence proliferated throughout the winter, travelling up the rhine all the way to Basel. The plague claimed the lives of many children, and was a cause of childbed sickness in young mothers. Various authors have speculated that this disease could have been scarlet fever. However, as with the previous post in greece, the descriptions for this disease are relatively vague.
The problem with these descriptions are the same as the ones I described in my previous post on hippocrates and the ancient Greeks. For nearly two thousand years, there had been little or no advances in the description and the treatments for this disease. However, had Johann Weyer been aware of advances in medical science occurring in Italy, he may have provided a far more rigourous identification of the plague of which he had been a witness.

The Renaissance had reached Italy nearly a century before northern Europe. Italy was the trade hub of europe, importing goods from the east to sell on to the west. And with these goods came various artisans and scholars, who helped to translate many works from Islamic scholars, as well as lost works from Ancient Greece.
Works of Galen reached Italy, and were taught in various schools of medicine. However, due to prohibitive laws on human dissection in Galen's time, much of his works were based on what he gleaned from dissecting barbary apes. Such was his repute that many of his claims on anatomy went unexamined for many years.
One man, Andries Van Wesel would change this. He approached anatomy from a more practical standpoint. He is known better by the latinized name he published under, Andreas Vesalius.
He was among the first people to perform human dissections. He pioneered a practical approach to teaching whilst he held a post at the University of Padua. He would get students involved in dissections. He is probably best know for the detailed images of human anatomy that populate his medical works. It was this culture of detail that he impressed upon his students, one of whom was a man from Palermo named Giovanni Filippo Ingrassia. Ingrassia already possessed a wealth of experience in the art of animal dissection, and had travelled to further his studies into human anatomy.

Vesalius's attention to anatomical detail is a lesson that Giovanni Ingrassius took to heart. After his studies, he returned to sicily, where he would work as a physician and lecturer, eventually contributing much to the literature. It was in 1553 whilst he was working as a physician that he published a book which contains a description of a disease he called “rossalia”. His detailed description of the etiology of this disorder indiciated beyond reasonable doubt that he was the first person to produce a stringent identification of the disease we now know as scarlet fever. Using his method of identification, it became possible to look at this as one disease, and distinguish it from others with similar symptoms, such as measles.
He eventually attained became the "protomedicus" of Sicily, placing him in charge of public health for the region. When the "Great Plague" described by Weyer reached the shores of Sicily, they were lucky to have a man as experienced as Ingrassius in charge. He recognised the contagious nature of disease, and frequently used isolation as a means of bringing it under control.
However, there was still yet more to be revealed about Ingrassia's rossalia, which we shall return to in the next post.

References:

Books:
"An historical account of the plague and other pestilential distempers which have appear'd in Europe ..." - 1722 Richard. Brookes

"An account of the sore throat, attended with ulcers: a disease which hath of late years appeared in this city, and in several parts of the nation" - 1748 John Fothergill

Journal articles:

Rolleston, J. (1928). THE HISTORY OF SCARLET FEVER BMJ, 2 (3542), 926-929 DOI: 10.1136/bmj.2.3542.926

Cappello F, Gerbino A, & Zummo G (2010). Giovanni Filippo Ingrassia: A five-hundred year-long lesson. Clinical anatomy (New York, N.Y.) PMID: 20803570

More Microbial phylomon

2011-08-20T15:44:00.002+01:00

More microbial phylomon !

We are Doomed- London Riots Edition

2011-08-09T02:35:00.003+01:00

#Scidoom
I alluded to many causes of our destruction in my comic of doom. I missed out the collapse of civilization, which is a shame considering that it is particularly apt for my current situation. London is burning as I write this.
Police have been unable to deal with the chaos.
People will tell you that it's been set off by the death of father of two Mark Duggan, who may or may not have been in possession of a converted replica gun, and may or may not have shot at police officers who definitely shot their own radio in the process. But this is by no means the whole story, which involves a lost youth with nothing to lose, an underfunded and demoralised police service and an economy in turmoil.

I'm currently aggregating news stories at my friend's non-science blog Ihatethisf**kingcity, and will write a better post on the London Riots once I can tie up the notes into a story, and once the fires have died down.

But if there is one thing I want to say at this minute, it's not a riot, it's the collapse of civil society.
to reiterate:

I'll be updating here. Its going to be a long night, and thankfully it's quiet where I am at the moment, and they haven't looted my coffee yet.

9/8/11- new updates can be found here. Better preparation,bigger police presence, should have more time to write a post on the origins of this catastrophe.

A History of Scarlet Fever: Beware of Ancient Greeks Bearing Diagnoses

2011-08-06T09:51:00.004+01:00

Regular readers may notice that I have a favourite bacterium, that I post on more than any other. This bacterium is known as Streptococcus pyogenes. My interest stems not only from the interesting ways in which it evades and bamboozles the immune system. It also comes from the weird diversity of infections that it causes. Not to mention that it once tried to kill me, and that I now study it for a living to get REVENGE.
I've decided to explore the history of the diseases caused by this bacteria, and how our understanding of them have changed over time. So let's start right to the beginning, in Ancient Greece.

The year is 430 B.C. and Athens was in the grip of war with its rival city state, Sparta. The war had reached its second year. Their leader, Pericles, had realised early on that facing Spartans on the battlefield would be suicidal.
Instead, he goaded them into attacking the city of Attica. When the Spartans took control of the city, they found it empty of people. They had all been evacuated to Athens, and whilst the Spartans had wasted their time securing the empty city of Attica, Pericles was pillaging unprotected spartan territory. Pericles strategy was a success, but there was one factor he didn't account for in his strategy. And this factor may have changed the outcome of the war.

An epidemic that had been proliferating in Ethiopia and Egypt had reached Greece. It probably started out as a few isolated cases in the countryside. However, when Pericles evacuated the inhabitants of cities into Athens, this changed. The city rapidly became overcrowded, and soon it was the perfect incubator for this plague.

"...people in good health were all of a sudden attacked by violent heats in the head, and redness and inflammation in the eyes, the inward parts, such as the throat or tongue, becoming bloody and emitting an unnatural and fetid breath.

"These symptoms were followed by sneezing and hoarseness, after which the pain soon reached the chest, and produced a hard cough. When it fixed in the stomach, it upset it; and discharges of bile of every kind...

Those who were ill were often abandoned, as carers would themselves be at high risk from contagion. Pericles himself was brought low by this disease. It had killed both of his sons, his wife, until eventually the plague killed him.
As the numbers of the dead increased, hundreds were piled into mass graves, whilst more were burned on funeral pyres.
The Spartan army, seeing the smoke from these pyres of Athens, pulled back. Whilst unassailable against any human foe, they knew better than to attack an infested city.

It is because of the writings of Thucydides that we know so much about this plague. He was one of the first writers to describe events based on facts alone, without invoking supernatural entities, or warping events to make a moral point. His detailed descriptions of the plague have lead many to speculate on the disease that caused it.
In the original first draft of this post, I was going to suggest that it may have been caused by a strain of scarlet fever, as others have in the past. Whilst this may have been the case, it is not the only suspect. Others have concluded that it was caused by some variant of the Ebola virus, whilst many believe it to have been an epidemic typhus.
The "plague of Athens" is the "Jack the ripper" case for epidemiology. This plague may have caused Athens to lose the Peloponnesian war, and the outcome of this war itself is blamed for the decline of Greece as a major power in the ancient world. This plague occupies an important place in history. Yet we can only speculate on the disease that caused it. The diversity of the diseases blamed for the plague indicates the true reason for this mystery. Thucydides descriptions of this plague are woefully insufficient to diagnose what caused it. However, had one of his contemporaries been present, it might have.

There had been schools of medicine in Greece for around two hundred years before Hippocrates was born. They borrowed from more ancient medical traditions in Egypt and Mesopotamia. These traditions were heavily based on superstition, with prayer to a divine entity forming a keystone of their treatment paradigm.
It was Hippocrates who changed this. Like Thucydides, he did not see the hands of the gods in every day events. He described diseases as natural phenomena, divorced from the supernatural. He and his students had a disciplined approach to medicine, which involved taking detailed observations on patients and their diseases.

During his life, and for some time afterwards he and his followers created the Hippocratic corpus, a collection of works and case studies that laid the foundation for modern medicine.
At sometime between 410-400 BC, the first in a series of works known simply as "Epidemics" were written. These consisted mostly of case studies, which contemporary physicians could use as reference to determine the prognosis for their patients.
Within these records, there is a description of an outbreak of a disease that caused a severe skin rash, along with a sore throat and fever. But these symptoms in themselves do not outright indicate that this was indeed scarlet fever. During this outbreaks, some of these patients experienced complications which are somewhat unique to Scarlet fever.

"in the most of them abscessed ended in suppurations, and there were great fallings off (sloughing) of the flesh, tendons, and bones;

The symptoms described here are very similar to necrotizing fasciitis
However, he descriptions written down in "epidemics" became the main reference for later generations of physicians when they described incidences of scarlet fever as they arose.
This legacy would persist for nearly two thousand years after. That is where I'll pick up the story in the next post

References
Books
Hippocrates Epidemics Part 2 - http://classics.mit.edu/Hippocrates/epidemics.2.ii.html

Journals

Rolleston, J. (1928). THE HISTORY OF SCARLET FEVER BMJ, 2 (3542), 926-929 DOI: 10.1136/bmj.2.3542.926

Descamps V, Aitken J, &; Lee MG (1994). Hippocrates on necrotising fasciitis. Lancet, 344 (8921) PMID: 7914656

Microbial Phylomon

2011-08-03T08:22:00.002+01:00

Picking up on a post on Lab Rat, I decided to quickly doodle some bacterial phylomon of my own for fun. Thus, I present GFAJ-1 , Streptococcus pyogenes, Bacillus anthracis,

Are We doomed?

2011-08-01T00:00:00.012+01:00

It's Silent. But is it Deadly ?

2011-07-21T20:32:00.010+01:00

Last February, an international controversy descended over the landlocked country of Malawi. The cause of this was a new bill about to be put forward that centred on the maintenance of clear air in public places.

Any person who vitiates the atmosphere in any place so as to make it noxious to the public to the health of persons in general dwelling or carrying on business in the neighbourhood or passing along a public way shall be guilty of a misdemeanour

This would prohibit smoking in public, the use of stinkbombs and outdoor barbecues. And more importantly, it could be interpreted as prohibiting public flatulence. That's right ! Citizens would be advised to clench hard or be prosecuted.
Surely this was a mistake ! No government would try to ban an involuntary physiological process. When pressed on this piece of legislation, the justice minister George Chaponda responded

"Government has a responsibility to ensure decency, Would you be happy to see people farting anyhow?"

He confirmed that the intent of this law was ban outbreaks of public flatulence. When news of this spread, Malawi became a worldwide laughing stock, and the bill was silently killed off. The then Justice Minister clearly disliked flatulence enough to support a draconian law against it. To be fair, is there anyone out there who actually likes the smell of flatulence?

Farts are unpleasant as a rule. I have yet to meet someone who, upon smelling a fart, inhales deeply and declares "mmm....Spicy ! "
But no matter how oleaginous, no matter how putrid, a fart has never killed anyone. Right?

The year is 1968. An outbreak of wound infections at Vanderbilt University Hospital was causing concern. The culprit, a bacterium known as Streptococcus pyogenes. This bacterium causes sore throats, skin problems and in the worst case scenario necrotizing fasciitis. A surgical wound infected with Streptococcus pyogenes can become life threatening.

So when nine patients contracted Streptococcus pyogenes infections during the month of august, there was a serious cause for concern. These patients had very little in common. They were operated on in different theatres. they were housed in different wards. In fact the only thing linking these patients was the anaesthetist attending them. He hadn't been ill with any of the disease associated with Streptococcus pyogenes. But it is possible for people to be asymptomatically colonised on their throats. So naturally they took throat swabs from him. They found nothing. There was no trace of Streptococcus pyogenes. So he couldn't possibly be the source of the infection.
The week after, another patient attended to by him developed a wound infection. This time they swabbed him again, in the throat and the nose. And again, all of these tests turned up negative. But taking no chances, he was prescribed a five day course of oral antibiotics anyway.
Despite this, during October, three more patients attended by this individual contracted the outbreak bacterium. The air in two operating theatres where this anaesthetist had attended tested positive for Streptococcus pyogenes.
An infection was found to have "took place in a room just vacated by the carrier". Yet this individual still tested negative for the outbreak bacterium. The staff at Vanderbilt were stymied. Where could the outbreak be coming from?

A similar case that had occurred at Washington University hospital two years previously held the answer. A similar outbreak had occurred, affecting eleven people. In this case, they had identified a carrier, who also mysteriously tested negative for Streptococcus pyogenes. In a desperate attempt to find out where he was harbouring this bacterium, they swabbed the following areas: Nose, Throat, Armpit, Groin, Teeth, ears, scalp, left foot, eyes, hands, anus and the right foot. They really did look everywhere, and they found the Streptococcus in an unexpected place. His rectum was teeming with Streptococcus pyogenes.

Upon finding about this case, the doctors at Vanderbilt decided to take a rectal swab from their suspected carrier. And they too found that the rectum contained the outbreak bacteria.

With this evidence in mind, it doesn't take a genius to figure out how the infection was spreading.

Whenever the anaesthetist expelled gas, Streptococus pyogenes was expelled along with it. The usually clean and sterile operating theatres became peppered with this dangerous bacterium. The course of oral antibiotics they gave the anaesthetist initially to clear the infection didn't work because they were targeted to his throat. Now they knew the exact source, they could give a more appropriate antibiotic treatment to completely clear the individual of this bacterium. He was relieved of his duties, and put on this course, after which he was completely clear of bacteria.

Luckily, thanks to the miracle of antibiotics, none of his patients actually died from these flatulence acquired infections. However we now live in times where more and more species of bacteria are becoming resistant to antibiotics, and perhaps we should reconsider reigning in our collective flatulence. If bacterial infections become untreatable, we may all need to "bung up" to prevent the spread of infectious diseases.

On a side note, Streptococcus pyogenes is also known as Group A streptococcus. Or GAS for short. Try reading through this article again with all instances of Streptococcus pyogenes replaced with GAS. It's confusing.

Schaffner W, Lefkowitz LB Jr, Goodman JS, & Koenig MG (1969). Hospital outbreak of infections with group a streptococci traced to an asymptomatic anal carrier. The New England journal of medicine, 280 (22), 1224-5 PMID: 4889553

McKee WM, Di Caprio JM, Roberts CE Jr, & Sherris JC (1966). Anal carriage as the probable source of a streptococcal epidemic. Lancet, 2 (7471), 1007-9 PMID: 4162660

Edit- At the time of writing this post, I was unaware of the anti-government protests and brutal crackdowns happening in Malawi. I have altered the tone of this article to be less supportive of the current oppressive regime.

Hello Field of Scientists !

2011-07-09T11:26:00.000+01:00

Old readers of this blog may have noticed a couple of changes to the design, domain name, and the little widget in the corner. This is because this blog has been accepted into the Field of Science network.
Double You, Zero Zero Tee !

To new readers, I should offer an introduction of some sort. This blog focuses on a number of different subjects, usually related to infection, with the occasional drawing or cartoon. I hope you enjoy reading this as much as I enjoy writing.

Links 04/06/11

2011-06-04T10:51:00.002+01:00

Hello, Gutentag and other such phrases.

You may notice in the next couple of weeks that there will be a complete lack of new posts. This is mostly because I have a few massive experiments set up for the next few weeks, that will absorb all of my energy.

But never mind that, there is plenty of other stuff on the internet that is worth reading.

Writing

Puffthemutantdragon.wordpress.com - Although it is very new, the first few posts are certainly worth a read. The style is long form, and the posts are notable not only because of their science coverage, but the coverage of the scientists themselves. It is because of this weaving together of fact and story that I recommend it as a cracking read. My favourite post so far is on the bubonic plague

Podcasts

http://www.psycho-babble.net/ I would like to say that I wasted an afternoon listening to the entire back catalogue of this podcast. But that would be a lie. I don't think that it was a waste of my time at all. It is funny, interesting and informative.

Webcomics

Gunnerkrigg Court - Probably one of the best webcomics out there, with tight plotting, great art and characterisation. Admittedly, it does happen to be a story about a person going to a mysterious schoo l.
But apart from that, it does occasionally deal with scientific themes as well as magical ones. If you want to know the one reason why I respect this comic are these three pages. I don't know many comics that are brave enough to give a balanced view of animal research, but apparently this is one of them.

Bugs, Drugs and Disease, and a Tale of Possible Terror Error?

2011-05-08T20:15:00.004+01:00

Last year, the UK was in the midst of an outbreak of anthrax, in which resulted in 47 infections, and 13 deaths. Bigger than the 2001 letter bomb attacks. Hospitals up and down the country were put on alert. The news media were notified, and the public were told of the dangers. But there was no panic amongst the general public. A case of the famous British stiff upper lip?
Not so much. This was not a terrorist attack. This was just another occupational hazard for heroin addicts.
These people were the victims of this outbreak. The drugs that they were injecting in their veins were contaminated with spores of anthrax.
To get to the source of this problem, we need to look at where the heroin itself is coming from. The main supplier of heroin to Europe for the past ten years is Afghanistan. Yes, that Afghanistan.

(I was inspired by Mitchell and Webb. see here )

It would be easy to jump to the conclusion that this was in some way related to terrorism. However, I personally don't believe this to be the case.
Nobody stepped up and admitted to causing this attack. And why would they? To out and out admit a connection to the sale of drugs would ultimately damage their support. If they were indeed targeting addicts, then they were vastly overestimating the compassion that the public has for these individuals. The panic and terror caused by this event was conspicuous by its absence.

So if this was not a terrorist attack, then what is the more likely way in which the anthrax got into the heroin supply?
The answer lies in the bug that causes Anthrax. We know anthrax as a terrifying biological weapon, but it is also a living micro-organism. It's been around longer than war itself. it has it's own life cycle, its own intentions that are separate from those who would use it as a weapon.

Bacillus anthracis is the bacterium that causes anthrax. It is a pernicious little bug, which can survive in soil for long periods of time. It can get stuck to grass, where it is eaten by a cow, sheep or other such creatures. It then multiplies, secreting virulence factors which ultimately lead to the death of the host, which can take weeks. over this time, the host can spread the bacteria over a wide area through faeces.

Ultimately, the bacteria kill the host, and as it decomposes, they re-enter the soil, ready to re-start their lethal life cycle.

These bacteria can then form highly tenacious spores that lie in wait for their next victim to accidentally graze them. Humans who come into contact with these animals or their leavings can become infected by this bacterium.

It has been found worldwide in various places. There is an area that researchers refer to as the "Anthrax Belt" which stretches from the Middle east into Central Asia. And bang in the middle of it are the poppy fields of Afghanistan. These poppy field, which may be fertilized with the manure from infected livestock. Or carried from these fields in leather sacks made from the skins of animals with anthrax.

The spores can tough it out through the various processes that turn the poppy plants into heroin.

And the desperate user injects this bacteria into their blood stream.

This is a terrible problem, but it is just one of the many terrifying bacterial infections which a heroin user will expose themselves to. Contaminated needles are known to spread MRSA, Streptococcus pyogenes, Pseudomonas, and this doesn't even count various terrifying viral infections like HIV. It's yet another hazard to which I.V. heroin users expose themselves.

Knox D, Murray G, Millar M, Hamilton D, Connor M, Ferdinand RD, & Jones GA (2011). Subcutaneous anthrax in three intravenous drug users: a new clinical diagnosis. The Journal of bone and joint surgery. British volume, 93 (3), 414-7 PMID: 21357967

Schmid, G., & Kaufmann, A. (2002). Anthrax in Europe: its epidemiology, clinical characteristics, and role in bioterrorism Clinical Microbiology and Infection, 8 (8), 479-488 DOI: 10.1046/j.1469-0691.2002.00500.x

Comic Journal Club: Was Hahnemann a Nostrum Vendor ?

2011-04-23T13:58:00.011+01:00

Whilst combing the old literature, I found this gem of a paper from 1859. Aa normal blog post would not do the job for this paper, so I made a mad decision. I decided to tell the story through the use of comic.

I fully recommend reading the original paper, as I have left out a lot of Gairdners more choice insults against Homeopathy.

Full size images can be found here:
Page 1
Page 2
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Gairdner, W. (1859). Was Hahnemann a Nostrum-Vendor? A Question of Fact BMJ, s4-1 (110), 101-102 DOI: 10.1136/bmj.s4-1.110.101

What the EHEC is that diagram of ?

2011-04-16T14:45:00.000+01:00

The history of science is peppered with great moments where people have gone above and beyond the call of duty in order to present their work in an accessible way. Think Florence Nightingale, and how she drew attention to the abominable conditions in hospitals through the use of a simple chart. Or perhaps Vesalius, and his intricate and detailed diagrams of the human anatomy.

The following paper deserves it's place among the greats, as it too has taken the graphical representation of science to a whole new level.

So what is this paper about?

The paper itself is about a bacterium known as Escherischia Coli, or E.coli for short. This species of bacterium lives in the digestive system of many animal species.

Not all E.coli are the same, and there is a diverse set of different strains of this bacteria, including ones that can cause disease. The focus of this paper is on Enterohaemorraghic E.coli serotype O157, or EHEC for short. EHEC causes bloody diarrhoea in humans, and hemolytic uremic syndrome. This is best known for regularly causing food outbreaks due to improperly cleaned meat.

It causes these diseases due to the way it attaches to cells in the large intestine. It has a set of genes, known as the LEE (Locus of Enterocyte Effacement), which causes the expression of proteins that force an attachment to the microvilli of the intestine. This attachment causes the microvilli to be severely damaged, and leads to diarrhoea.

Like many bacteria that cause disease in humans, EHEC does it because it doesn't necessarily belong in the human digestive tract. The LEE, which make it cause this disease in humans, are actually essential to its survival in it's natural host: the humble cow.

The cow's digestive system is far more complex than the human one, containing a stomach with four compartments, and a variety of different commensal bacteria to aid with digestion. Here, the EHEC's specific niche within the cow is at the reticulo-anal junction. When it gets there, it can express it's attachment genes in this area without causing the cow the slightest bit of discomfort.

In order to get there though, it has to run through the acidic compartments of the stomach. But this bacteria doesn't have any idea of when it's going to have to cope with stomach acids. Nor does it have any idea of when it reaches the recto-anal-junction.

What it does to work these out is quite clever. The first compartment of the stomach the EHEC encounters is the rumen. This is home to lots of other bacteria, which help the cow break down the tough cellulose in grass.

These bacteria are in constant communication with eachother, using bacterial pheromones. These compounds are called Acyl-Homoserine Lactones, or AHL's for short. The rumen is choc full of them. Whilst the EHEC doesn't produce any of these chemicals itself, it can sense their presence using a regulatory gene called sdiA.

This regulatory gene tells the bacteria when it can express it's attachment proteins.

If AHL's are present, they will filter into the EHEC, and when they bind the SdiA protein, it undergoes a transformation that allows it to do two things:

1. It will sit on the DNA encoding the LEE, preventing it being read. This stops the attachment proteins being made.

2. It force other proteins to activate a gene called gad, which encodes acid resistance genes, and it will ensure that it is transcribed more. This will make the cell more resistant to acid.

So what do these two things mean?

Well, the diagram of a cow pictured below will explain:

In the rumen, where there is lots of AHL's present, the genes encoding the LEE are repressed, whilst the genes encoding gad are upregulated. This prevents the bacteria sticking to the wrong place of the stomach, where there is high competition, and also prepares it for the environments within the acidic stomachs,
However, as it travels though the digestive system of the cow, the amount of AHLs decrease, until you get to the recto-anal junction. Here there are no AHL's, and so the LEE genes can be expressed, allowing for the bacteria to attach to this area.

So why do I think this diagram has a place in history?
This is not just a functional representation of a cow's intestine. That could be achieved with a series of boxes drawn in microsoft word, with arrows between them. It goes beyond simple information communication, and moves towards high art.
This is an impressionistic interpretation of a cow, but not from a human perspective. In fact, I'm not even sure it's from a bacterial perspective. It is from the prespective of the SdiA protein itself. it's most important function, within the rumen is most prominent. As the artist traces out the rest of the digestive tract, the lines become more wavy, more chaotic. Perhaps this represents how the gene itself loses a sense of itself after it passes through the acidic regions of the stomach. It only knows where it is by what isn't there, a truly confusing state of being. But when guides its bacteria to its location, a truly amazing celebration occurs, resulting in a blue plume which must represent something or other.

Sperandio, V. (2010). SdiA sensing of acyl-homoserine lactones by enterohemorrhagic E.coli (EHEC) serotype O157:H7 in the bovine rumen
Gut Microbes, 1 (6), 432-435 DOI: 10.4161/gmic.1.6.14177