Mouse with a view

Take a look inside: a new implant allows researchers to observe the development of lung cancer in a living, breathing mouse.
Take a look inside: a new implant allows researchers to observe the development of lung cancer in a living, breathing mouse.
Credit: Entenberg et al.

In one of history’s more unplanned career choices, in 1822 a young man called Alexis St Martin was forced to swap a life as a fur trapper in the US state of Michigan for another as a doctor’s assistant.

The catalyst for the change was a brutal – indeed, near fatal – bullet wound to the abdomen. The injury was by all reports appalling, leaving a huge hole in poor Alexis’s side and ripping away a significant part of his stomach.

By the time the injured young man was delivered into the mercies of William Beaumont, an army doctor, he wasn’t expected to survive for more than another few hours.

But survive he did, thanks to several no doubt painful surgeries conducted by Beaumont over a period of weeks. Indeed, after a while, the one thing the doctor had left to do was sew up the wound – but St Martin’s patience was finally at an end and he refused to go under the needle ever again.

The result was an ex-fur trapper with a big hole where the side of his trunk should be and a see-through stomach. The hole no doubt looked awful, but was apparently quite sterile – any infection arising from the gun wound and subsequent exposure effectively neutralised by his own stomach acid.

St Martin was clearly no longer suited to a life roaming through the boondocks (not with all that goop slopping about every time he moved) so Beaumont gave him a job as a handyman.

The doctor soon realised his assistant had a different, more valuable role to play: for the next several years Beaumont meticulously documented the way in which St Martin digested food. He also took samples of the liquids in his stomach and sent them off for analysis – discovering, in the process, that hydrochloric acid was central to how digestion operated.

In a new report published in the journal Nature, the distant memory of the fur trapper with the hole in his abdomen is rekindled, albeit in a rather different and rather more intentional fashion.

A team of scientists led by David Entenberg of the Einstein School of Medicine in New York, US, report the development of a permanent implantable window designed to fit over the lung of lab mice bred to develop lung cancer. The window – small and round – allows researchers to watch and record to the growth of the tumour for weeks on end.

The invention, the researchers note, is a vast improvement on existing techniques for obtaining high-resolution images of a living mouse lung. This involves using   ventilator, removing the rib cage and then holding the lung tissue still in a vacuum.

“As such,” the authors note, “they are extremely invasive, terminal surgeries which are limited in duration and do not allow more than one imaging session.”

It is clearly less than optimal to use an imaging technique that kills a mouse before it dies of cancer, and Entenberg’s team appear to have come up with a much less damaging solution.

Implanting the window, they write, “allows the mouse to survive surgery, recover from anaesthesia, and breathe independently.”

Dubbed the WHIRL – “window for high-resolution imaging of the lung” — the mouse-with-a-view, the scientists conclude, “gives researchers this ability to directly visualise tumour cell arrival and ultimate fate during spontaneous metastatic progression over weeks, and this enables investigations into the mechanisms underlying tumour cell seeding, survival, dormancy, and growth.”

William Beaumont, you get the feeling, would have been impressed. Alexis St Martin, perhaps less so.

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