Friday, 13 July 2012

Could Flowers for Algernon really happen?

Have you read the book Flowers for Algernon?

There is a paper by Konopka et al., which describes the mice that recapitulate Algernon’s (and the protagonist’s) fate.

These mice were genetically modified in an interesting way. Namely, they have a molecular “switch” in the brain, that upon addition of a drug (tamoxifen), causes them to turn off a gene. This gene produces a protein that directs making of micro RNAs, small RNA particles that regulate pretty much almost everything. To simplify, the small RNAs keep down the production of many proteins responsible for learning. When we turn them off, the production goes up.

The process is gradual. Micro RNAs are very stable in the brain. Only several weeks after having a gene turned off the mice have started to experience some effects. And surprisingly, as some brain protein levels were rising, the mice were getting smarter.

There is a lot of tests to examine how smart a mouse actually is. They aren’t perfect, because these tests were originally designed for rats, and rats are much more intelligent. A mouse is generally a dumb animal, and doesn’t socialize as well with humans, so it’s harder to make it learn.

For example, take the Morris water maze test. Basically what you do is that you let a mouse into a water pool. Mice can swim, but they don’t like getting wet. The only way to get away from the water is to find an invisible platform and step on it. The first time, a mouse finds it by exploring. For several days, the mouse is learning where it is, so she gets there gradually faster.

This way we can compare mice lacking a gene and normal mice and see how fast they learn. This is a very good test… unless the mice don’t want to learn. Because, for example, they come from a dumber strain. Of because they don’t like the experimenter’s scent, or there are two different experimenters and the mice are confused. I’ve even heard that water’s temperature can be an issue. When it’s too cold, a mouse will be too uncomfortable to explore and just swim in circles. When it is too pleasant for the mouse, it will delay searching the platform and float on the water, having fun.

Altogether, behavioral testing is a pain in the ass, or so I’ve been told, because so far I’ve been mostly doing molecular research.

So you take these mice, run a battery of test, and each one of them shows a different aspect of a mouse learning. At the end of the story you have a pretty good idea of how smart your mice are. It takes time. And if your experiment doesn’t work – for the reasons mentioned above or more – you repeat that. Then you have to repeat that once again. After all, this particular mouse could be just smart by accident. To fulfill the minimum for a publishable experiment, you must repeat it at least three times. Not – three mice. Three groups of mice, one after another, preferably each from a new litter.

Mice live up to two years, and they start to age at approximately seven months. By the time you have finished all the tests, your first litter of genetically modified mice has probably gotten old. Anyway if this is a new strain, you want to see how they age.

In the case of the paper I’m writing about, the researchers already knew that these mice age badly. After the intelligence boost, when they lose all the miRNAs, they experience neurodegeneration. Just like in the “Flowers for Algernon” – first they get smart, and then decline with devastating effects, only it was discovered in a reverse order.

You can’t get genetically modified humans. But what if the experiment was about a therapy, a drug or an operation, like in the novel? Could Flowers for Algernon happen in real life?

There was just one mouse in the book. If I recall correctly, the experiment wasn’t even repeated before they applied it on a human. Mice age fast – the scientists in the book would have noticed something before even thinking about human tests. They wouldn’t even have to wait on purpose. It’s impossible to do all the tests that were done on Algernon, then some additional experiments to support it, describe it all, show it to the press and publish without the mouse getting old. The reviewers would make them create more mice like Algernon. They would make them dissect Algernon’s brain and investigate the slices. This paper would get stuck in a publishing hell!

Or maybe that was feasible several decades ago, when the book was written? Maybe the rules weren’t that restrictive, but the media weren’t that fast, too.

Therefore I have no clear answer. And I do wonder.

No comments:

Post a Comment