Mobile laboratories, champagne and silver nitrate

I’ve been trying to get my head around what the actual day-to-day nursing of a dysentery patient would have looked like – and the relationship between the nurses at the Casualty Clearing Stations with the bacteriologists. What the nurses understood of the bacteriology, their relationship to the process of diagnosis etc etc. 

I’ve been reading an article by a guy called Robert Atenstaedt about the development of bacteriology (full citation below). He talks about the British going into the Crimean War with such a tiny, unprepared medical team (old soldiers who couldn't carry themselves let alone patients). It was the first war after Telegraph was invented, and the immediacy of the news about soldiers suffering (from dysentery amongst other things) generated outrage at home. That outrage drove the creation of the medical corps. It makes me think of learning about Vietnam, the televised war. It also puts Florence Nightingale in context.

He goes on to say that, despite new knowledge, bacteriologists in WW1 were considered low status - it was routine water testing. Anyone with medical training was wanted for what was felt to be more important work. So it makes sense that Sister Williams was able to carve a niche for herself as a bacteriologist. 

 And now it comes to the link between the bacteriologists and the nurses.

Briony, seeking the Wellcome Library online catalogue has found the Mobile Laboratory. We were scanning through a whole screen of thumbnails and suddenly it was there. This image, I nearly squealed.

Atenstaedt describes the first one, quoting :

a motor vehicle was fitted out with all the pathology paraphernalia of the day including microscopes, centrifuges, autoclaves and incubators: 'The inside of this multum-in-parvo thing on wheels was equipped with everything that the heart of a bacteriologist would require’

(if you’re wondering what multum-in-parvo means, it’s ‘much in little” - ie. the old school way of saying ‘tardis’).

He says there were 15 mobile laboratories built, and each had a two-seater cycle car for collecting specimens. I love the two-seater cycle car. It’s our physical link between the nurses and the laboratory. It's the pathway the samples take. 

A woman called Rachel at the British Royal College of Nursing helped me out, showing my how to search their archive. British Journal of Nursing has some fabulous articles about the treatment of dysentery. Some highlights: 

A SEVERE CASE OF DYSENTERY (Dec 1915)

The feeding of the patient from October 22nd to 26th consisted of small quantities of albumin water, egg-flip, jelly, brandy, and champagne, given every two hours

and

WHAT ARE THE CAUSES OF DYSENTERY, AND HOW IS IT TREATED? (a prize winning paper by Miss Bessie Grey Johnson 1917)

The patient should be kept warm in bed, and should use the bedpan for all evacuations... If there is not too much tenesmus, rectal injections of either of the following solutions, as prescribed, warmed to 100' F., should be allowed to run slowly into the bowel from a funnel through a long soft tube :- Boric acid, I drachm to I pint. Nitrate of silver, 5 or 10grains to I pint. Quinine, 10grains to I pint.

I read these aloud to Gregory and Briony who gasp and giggle and at one point Gregory muttered, “Pure witchcraft”.

Another prize winning article is all my heart desires: WHAT PRECAUTIONS WOULD YOU TAKE IN SAVING FOR MICROSCOPIC EXAMINATION, A SPECIMEN OF URINE, A SPECIMEN OF SPUTUM, A SPECIMEN OF FAECES? 

I still have a lot of questions. I want to know who drove the cycle car? Who ordered the specimens? Where did the nurses store them? How far did the mobile laboratories travel? And who emptied the bedpans...

Atenstaedt article details:

"The Development of Bacteriology, Sanitation Science and Allied Research in the British Army 1850-1918: Equipping the RAMC for War by RL Atenstaedt (JR Army Med Corps 156 (3): 154-158) 

Meet the Scientists: Dr François-Xavier Weill

François-Xavier Weill is one of those rare truly interdisciplinary researchers: one part Microbiologist, one part Historian and one part Epidemiologist.

His work mainly focuses on the evolution, emergence and detection of new strains of enteric pathogens (which basically includes the nastier versions of Salmonella, Shigella, Vibrio and E. coli) around the different human populations on Earth…so that we can better understand how, when and why enteric diseases spread.

Of particular interest to our research, was François-Xavier’s focus for several years on the epidemiological mapping of large numbers of different Shigella species around the globe over the 100-odd years. This (currently) unpublished research specifically shows which Shigella species were prevalent during WWI and suggests how they might have moved around the globe during the war. We’ll link to the article highlighting this amazing body of work when it appears in late 2015!

Briony, Ailsa and I travelled out to Cambridge (UK) to meet with François-Xavier in his home...stopping to admire the punts along the river Cam.

In our highly caffeinated meeting, our discussions included:

• the role of nutrition in affecting the acidity of the stomach – lowering the defenses of soldiers and nurses to dysentery;
• the high similarity between E. coli and Shigella (something Kat Holt had also mentioned) – Shigella is essentially a weaponised E. coli, adapted to infect and rapidly multiply in humans;
• the change from Shigella dysenteriae to Shigella flexneri with improved hygiene, corresponding with the modern understanding of how S. dysenteriae wreaked havoc in the god-awful conditions in Gallipoli to the lesser incidence of S. flexneri in the much improved (and less tropical) trenches on the Western Front;
• how the identity of the dysentery-causing agents were strongly contested in the early 20th century – with many scientists insisting that amoebic dysentery (caused by the amoeba Entamoeba histolytica) was the only significant disease;
• how the high morbidity of bacillary dysentery (that is, dysentery caused by the Shigella bacillus) created such a high burden to the resourcing of the war, considering the need for intensive nursing of each infected soldier over a period of several days to weeks;
• the difficulty in studying dysentery, given that there are no animal models – that is, disease-causing Shigella only infect humans – and it’s never easy to experiment on humans…
• and finally what sensitive creatures Shigella really are, especially outside of their niche in the large intestine!

François-Xavier also made the interesting suggestion that we consider using Shigella dysenteriae type 1 as the anti-hero in our story, due to its ability to make the deadly Shiga toxin…although this presents other new difficulties to our current storyline!

Meet the Scientists: Dr. Laurent Debarbieux

The phage whisperer…

While in Paris, Ailsa, Briony and I travelled out to the Institut Pasteur to meet with Dr. Laurent Debarbieux – an expert on Bacteriophages – that is, viruses that infect bacteria. Laurent works at the forefront of research into using bacteriophages to attack and destroy particularly difficult bacterial infections, such as cystic fibrosis infections in the lungs. And while the results have been promising, there is still much work to be done to determine whether bacteriophages can be used reliably to treat clinical infections. At the same time, scientists like Laurent also need to convince our medical and public health authorities to consider the possibilities of using viruses as allies against particularly nasty bacteria! But with the current crisis in antibiotics, the stakes couldn’t be higher!

We had an amazing session discussing bacteriophages with Laurent, hearing his perspectives about how bacteriophages can adapt to infect new host bacteria. In particular, we picked his brains about the scientific creation of our story’s viral hero...

Meet the Scientists: Prof. Philippe Sansonetti

Pasteur-ising

How could a trip to Paris be complete without paying homage to Louis Pasteur?

First up, Briony and I visited the Museé Pasteur – a museum dedicated to the legacy of the man who discovered the role of microbes in fermentation, created vaccines for rabies and anthrax and much, much more.

Since the time of Aristotle, it was thought that many life forms spontaneously emerged from water, dust, rotting flesh or the aether. But Pasteur championed the idea of biogenesis (Omne vivum ex vivo "all life from life"), famously demonstrating that sterilised meat will not rot without exposure to microbes from the surrounding air (luckily, he didn’t try that experiment with a McDonalds burger).

Pasteur also famously showed that microbes were responsible for spoiling beverages such as milk, beer and wine – and invented the process of pasteurisation – where the heating of these liquids killed most bacteria and moulds, preventing the potential growth of spoiling or disease-causing microbes.

The creation of the anthrax and rabies vaccines brought great wealth to Pasteur, and led to the creation of the Institut Pasteur  - dedicated to the study of microbes. Still to this day, the Pasteur Institute is a world leader in the research of microbes, particularly their role in disease. And it was here at the Institut Pasteur, that we were to encounter Professor Philippe Sansonetti.

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Sansonetti vs Shigella

The anti-hero in our upcoming book The Invisible War is Shigella flexneri, the bacterium responsible for most of the dysentery (severe diarrhoea) in the trenches during WWI.

While S. flexneri still causes millions of cases of dysentery in the poorest societies on Earth each year, we now understand a lot more about how it causes dysentery – in no small part due to Professor Sansonetti.

The thing that makes all Shigella bacteria so pathogenic (that is, able to cause disease) in humans, is the ability for a very small number of Shigella cells to invade our intestinal epithelium (the wall of our gut). And once inside, these Shigella can take over our epithelial cells – stealing our energy and assimilating our building blocks to make billions more…causing continuous eruptions from our gut wall to invade new regions of our intestine. This process releases lots of blood, which mixes with the eruptions of our intestinal mucus (trying to flush them away), to create bloody, mucous stools – characteristic of dysentery!

Working on Shigella for over 30 years, Prof. Sansonetti has provided the most complete and unified view of any bacterial-controlled disease process. Perhaps not surprisingly, these discoveries are now being employed to develop a vaccine against different types of Shigella still causing illnesses and deaths around the world every day.

We sat down with Philippe to learn more about his discoveries into how Shigella cells invade the human gut epithelium and how they take over once inside – so that we were best able to describe this process in our story. Probably the most interesting thing we learned about was how Shigella bacteria can trigger the ruffling of an adjacent intestinal cell (see above image), a process of engulfing which essentially ‘tricks’ our intestine into swallowing and internalising the Shigella…after which, all hell breaks loose!

Researching "The Invisible War" - Meeting the computational biologist

Cycled down through a blustery Melbourne afternoon (no gloves, cold fingers) to meet Kathryn Holt at the Bio 21 Institute. She found us a spot on Flemington Road to have coffee and Gregory asked, “So, do you know why we asked to meet you?”

She shook her head, smiling quietly and I wondered if she thought we were a bit crazy. Gregory pulled out copies of Squid Vibrio and Zobi and launched into a description of Mission Symbiosis Storytelling.

Kathryn explained to me that she’s a computational biologist – which I had never heard of. There’s something kind of amazing and on the edge of humiliating about being the absolute novice thrown into these conversations. Kathryn talked me through it.

She’s working with samples of the Shigella bacteria, which causes dysentery (some of which are over a 100 years old, from WW1. Think of them sampling soldiers’ stools and keeping those samples intact for so long). Kathryn does genetic analysis and uses that information to trace where Shigella bacteria have travelled in the world. She told us about a guy from the Pasteur institute, who’s obsessively using genetic data to exactly track the movement of Shigella bacteria from trench to trench during the war. I love the stories I get to hear of humans dedicated to drilling down such specific details.

Kathryn talked about the Shigella bacteria’s “type three secretion system”. The they have 40 or 50 genes which can form the shape of a needle used to puncture a human gut wall. Then they manipulate our cells so they can live inside them. Her descriptions were so graphic. I was already seeing scenes of our story forming.

She talked about the microbiome, the thousands of species of bacteria in our gut, some of which would compete with Shigella, helping us to beat the dysentery.

I sat there, cold hands gripping my coffee, listening with a kind of gleeful astonishment.

The last thing I wrote in my notebook for that meeting was, “macrophages patrolling your gut”.

The Squid, the Vibrio & the Moon eBook Launch: A Poem

Making an eBook is really quite tough,

there are so many stages between finished and rough.

View fullsize

But with so many people willing to help out,

we have finally made it to the part where we shout.

First of all, I will thank the microbes,

without whom our story would not have grown.

There are scientists, writers and artists to mention,

all inspired by invisible micro-dimensions.

Symbiotic relations between small and big,

in this case between Vibrio and a much larger squid.

When the storybook was printed, we made it a square,

but this is not a good shape for iPads to wear!

So Mark our designer took a good hard look,

and lo and behold, a rectangular eBook!

Next comes the task of spreading the word,

thank you to Cameron who has helped make us heard.

And to everyone who has and will share our tale,

thank you for acknowledging the smaller scale.

The role of our small friends and the part they play,

is too large to mention in one book or one day.

One thing however I'll say in this post,

they can sure work together...that's what I like most.

http://www.smallfriendsbooks.com/squid-vibrio-moon/

Meet the Scientists: Dr. Jeremy Barr

The main stimulus for The Invisible War came from an article by Jeremy Barr “Bacteriophage adhering to mucus provide a non–host-derived immunity”, published in the prestigious US journal PNAS in June 2013.

Here, Jeremy, along with group leader Forest Rohwer, writer Merry Youle and other co-authors described a mutual symbiosis between mucus-producing (animal) “host” with their phage partners – where the virus partner limits mucosal bacteria, while the animal host presents new bacterial hosts in the mucus for the phage to reproduce.

The enemy of my enemy is a phage

Widely hailed as the discovery of a new immune system, we knew we had to speak to Jeremy Barr about the potential to describe this newly symbiotic relationship as a story in our series. We were overwhelmed by Jeremy’s enthusiasm about collaborating to communicate this discovery as widely as possible.

Jeremy also had an implicit understanding about the power of using narrative to engage people in a topic, something at the heart of our mission. One of our extra incentives for creating this particular story was the challenge of writing a story with a virus as a hero…something we hadn’t anticipated at the start of our process of creating Small Friends stories!