(Not quite) the Battle of Cannae, in miniature

This is an essay that I originally wrote for the Wellcome Trust Science Writing Prize competition in May 2011. It was not short-listed and I’ve been meaning to publish it here for a some time. Like the new paintings I’m making, this piece attempts to describe a molecular mechanism by using allegory so that the process can be more easily understood.

In the early years of the twentieth century, outbreaks of typhoid fever mysteriously appeared among wealthy households in the New York area. The cause? Their cook, Mary Mallon: the first recorded healthy carrier of a disease. ‘Typhoid Mary’, as she came to be known, had a deadly strain of Salmonella living in her gall bladder, shedding infectious particles into her faeces. Although she wasn’t sick, those she cooked for certainly were.

Salmonella bacteria enter the human body through our mouths, often in contaminated food. A tactical military commander surveys the ground before luring an opposing army to battle, orienting their opponents in such a way that they may be blinded by the morning sunlight and by dust blown across the battlefield by the prevailing winds. Similarly, the human body makes use of its terrain as a natural deterrent to potential invaders: Salmonella finds itself in a giant acid bath, otherwise optimised for decomposition of the food we eat.

The stomach, however, is no match for the advancing Salmonella. Any acid leaking into the bacterial cell is promptly used to modify distinct molecules the bacteria finds around itself (conveniently products of protein digestion, a plentiful resource in the stomach). The modified protein products are rapidly dispatched back into the stomach, maintaining the interior of Salmonella less acidic than the stomach, so protecting their precious internal components from harm. Still the Salmonella advances, on to the small intestine.

Through the cells lining the small intestine, the Salmonella reaches the blood, a liquid highway able to take it anywhere it desires to go. Macrophages – quite literally ‘big eaters’ – form another of the body’s front line defenses against intruders. They may be stationed at distinct sites, such as the liver or spleen, or more widely roam the body, engulfing any material that they come into contact with.

The double envelopment tactic was used by Hannibal to great effect at the Battle of Cannae in the third century BC. As the Roman army advanced they believed they had the advantage, having backed Hannibal’s Carthaginians up against the Aufidus River. Cunningly though, Hannibal lengthened his infantry line, ordering his African troops around the sides of the more numerous Roman infantry. The Carthaginian cavalry came at the Roman infantry from behind, fresh from defeating the weaker Roman cavalry. The Romans found themselves encircled.

The Battle of Cannae, Ernesto Reiner http://www.reiner.org/

Like Hannibal’s army, as the macrophage membrane contacts a hostile microbe it drops back, surrounding and enveloping the organism until the membrane is pinched off and the microbe completely enclosed in a tight compartment within the macrophage cell. The Romans were completely surrounded, enabling Hannibal’s army to focus their weaponry for maximal effect; those that weren’t killed by the cutting swords or piercing spears were crushed and suffocated by their neighbours in the struggle. The macrophage weaponry constitutes destructive oxygen species, acid and highly charged anti-microbial molecules. The Roman army was completely defeated with massive loss of life; the macrophage obliterates its target, digesting it and presenting a small component of it on its surface like a battle trophy.

Salmonella bacteria, however, have different ideas. The more virulent strains, like those causing typhoid fever, may actively encourage engulfment by macrophages. It seems that Salmonella find the internalised compartment in a macrophage a most inviting place to live and reproduce. Of course, the constant barrage of damaging chemicals could be tiresome, but these bacteria have evolved their own counter-defences. They produce chemicals that bind and chop up the positively-charged anti-microbial molecules in their milieu to prevent the molecules from getting too close.  Against those that do pass, they put up extra shielding and change the characteristics of their outer membrane to prevent the positively-charged molecules from reaching their inner membrane where they will punch holes like a sword or spear. The toxic oxygen species and degrading chemicals are delivered to the invader in small packets, yet somehow Salmonella is able to prevent the arrival of these. In fact, it seems these bacteria actively remodel the interior compartment of the macrophage to allow them to live and multiply in comfort, protected from the rest of the body’s defences.

When the Salmonella bacteria have produced sufficient reinforcements they burst from their macrophage hiding place, drawing much attention to themselves. If they’ve riled the human body enough, they can ride a wave of vomit or diarrhoea out to infect a new host. It’s hardly surprising that Typhoid Mary could not be convinced that she was the one infecting the households she worked for. How could she be so well yet spread such a destructive disease?

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