Thursday, September 1, 2016

gnotobiotic: the woes of a germ-free organism


guardian |  Peering inside one of these chambers, I met the eyes of one of the strangest animals on the planet. It looked like just a mouse, and that is precisely why it was so weird. It was just a mouse, and nothing more.

Almost every other animal on Earth, whether centipede or crocodile, flatworm or flamingo, hippo or human, is a teeming mass of bacteria and other microbes. Each of these miniature communities is known as a microbiome. Every human hosts a microbiome consisting of some 39 trillion microbes, roughly one for each of their own cells. Every ant in a colony is a colony itself. Every resident in a zoo is a zoo in its own right. Even the simplest of animals such as sponges, whose static bodies are never more than a few cells thick, are home to thriving microbiomes.

But not the mice in Gordon’s lab. They spend their entire lives separated from the outside world, and from microbes. Their isolators contain everything they need: drinking water, brown nuggets of chow, straw chips for bedding, and a white styrofoam hutch for mating in privacy. Gordon’s team irradiates all of these items to sterilise them before piling them into loading cylinders. They sterilise the cylinders by steaming them at a high temperature and pressure, before hooking them to portholes in the back of the isolators, using connecting sleeves that they also sterilise.

It is laborious work, but it ensures that the mice are born into a world without microbes, and grow up without microbial contact. The term for this is “gnotobiosis”, from the Greek for “known life”. We know exactly what lives in these animals – which is nothing. Unlike every other mouse on the planet, each of these rodents is a mouse and nothing more. An empty vessel. A silhouette, unfilled. An ecosystem of one.

Each isolator had a pair of black rubber gloves affixed to two portholes, through which the researchers could manipulate what was inside. The gloves were thick. When I stuck my hands in, I quickly started sweating.

I awkwardly picked up one of the mice. It sat snugly on my palm, white-furred and pink-eyed. It was a strange feeling: I was holding this animal but only via two black protrusions into its hermetically sealed world. It was sitting on me and yet completely separated from me. When I had shaken hands with Gordon earlier, we had exchanged microbes. When I stroked this mouse, we exchanged nothing.
The mouse seemed normal, but it was not. Growing up without microbes, its gut had not developed properly – it had less surface area for absorbing nutrients, its walls were leakier, it renewed itself at a slower pace, and the blood vessels that supplied it with nutrients were sparse. The rest of its body hadn’t fared much better. Compared with its normal microbe-laden peers, its bones were weaker, its immune system was compromised, and it probably behaved differently too. It was, as microbiologist Theodor Rosebury once wrote, “a miserable creature, seeming at nearly every point to require an artificial substitute for the germs [it] lacks”.

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