No Mouse? No Más!

It’s difficult to know how often opportunities to change the way that an entire system of knowledge makes sense of the world really come along. By their nature, most human systems tend toward a state where reproducing the way things becomes deeply insinuated into whatever the system was intended to do. Practices turn into “the way it’s done.” Any reader can list his or her own favorite personal, professional, or historical examples, not to mention all of those within which we’re probably sitting comfortably right now.

One ready-to-hand example comes from the National section of today’s New York Times. Gina Kolata reports on a recently-published study that demonstrates some likely limitations of contemporary science’s preferred laboratory stand-in for human subjects: the mouse. It’s about the use of mice in the study of sepsis, but likely has consequences for other diseases. Short version: although mice and humans have enough in common genetically that successful tests of treatments on the one correlate with successful medical treatments on the other, where there are differences the differences really matter.

The research study here, though, had its genesis in another study by the same research team that sampled humans rather than mice. Those research questions were, for what genomic science can do today, pretty straightforward. What are the white blood cells of patients with sepsis (or trauma or severe burns) doing at the genetic level? What genes are operating, and in what combinations? By the article’s description, the researchers amassed a data set that would be the envy of anyone. But peer-reviewed publications rejected the study because the findings had not also been replicated in mouse studies.

I have to hand it to the researchers, for the next thing they did was ask themselves: What does happen in mice in situations like this? And while the article doesn’t really spend a lot of time on this part of the story, here is where I find the most interesting pivot point. They asked this question because they accepted the validity of the premise. No mouse? No más. So let’s get some mice on this.

“The group decided to look,” Kolata writes, “expecting to find some similarities. But when the data were analyzed, there were none at all.” And it unfolded from there that mice are highly resistant to the things that lead to sepsis in humans.

(At an earlier point in the article, it’s mentioned that mice are susceptible to something that resembles but is not sepsis, the implication being that the assumed similarity translated to an assumption at the level of medical understanding and clinical care.)

And so then, when the researchers turned this new finding into a paper and submitted it for review, they once again ran into the embedded assumption about mice. Rejection. Not on the basis of scientific error, but rather, as one of the lead authors characterizes reviewers’ responses, “It has to be wrong. I don’t know why it is wrong, but it has to be wrong.”

The story includes a lot of the typical features of this kind of narrative: a grounding assumption, systems of sifting and winnowing knowledge that sort on the basis of that assumption, protective gatekeepers who seem to set aside common sense in favor of what the record says should be the case. On the plus side, I see throughout one of the greatest strengths that those who do public engagement and scientific outreach can master: the value of narrowly defined claims, scope, reach, and implications. As well, it’s extremely positive that wired state of the world makes it possible for research to be widely actionable because the scope and speed of possible reception are wide and quick.

Here, the researchers were also fortunate that the grounding assumption they violated was above the surface of disciplinary knowledge where they could see it. It’s also worth noting that they could, after the first round of rejections, pivot rapidly to add a mouse component to their study. The second round of rejections is where they ventured into much more unsurfaced territory. I don’t know why it’s wrong, but it’s wrong — that kind of formation is a signal that you’re close to the heart of something very powerful. The closer you get to an unexamined but incredibly high-value assumption, the more correct you’d best come. Because it will be on.

So. No mouse: no más? Hopefully no more.

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About David D. LaCroix

Learning and education strategist; Director of Operations at Versatile PhD. All opinions expressed here are my own and do not represent those of my clients, partners, or employers.
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