Gray Matters: Scaring mice for fun?

Coming to Lehigh, some of my top interests were: addiction and personality, mood disorders and learning.

I was stupid enough to think I should major in computer science. I did mental gymnastics to justify to myself how I could address some of the issues I find most exciting with a bachelor’s degree in blue light and G-Fuel.

But eventually, I came around to behavioral neuroscience — a degree in a single organ, government funding and hospital lights.

Further, I was ridiculously lucky to be involved in a lab where I could address any one of these issues, and in a bit of time, in any way that I want to.

Right now, I’m working with mice that have a particular gene removed. This gene regulates anxiety modulation in the amygdala. To keep a genetically-modified-horror-story short, these mice experience higher levels of anxiety than regular mice.

Each time I’ve held one of these mice, I feel a weird kinship with them for this reason. They’re all jumpy and bitey and defensive, and I realize that if I’m a mouse, I’m these mice.

Despite this being an excellent and creative opening for a graduate school application essay, I also found myself recently thinking about how and when scientists started using animal models in research, particularly mice.

Animal testing goes back about as far as academia does. In the fourth and third centuries B.C.E., Aristotle and Erasistratus were among the first to perform documented experiments on non-human animals.

However, there is even anthropological evidence that within 3400-3000 B.C., a Neolithic surgeon drilled a hole in a cow’s head. This practice is called “trepanation,” and it seemed to be shockingly popular, with five to ten percent of human skulls found from the Neolithic period having holes in them.

Then, as we go forward in time, there are several examples of people who dissected and documented animals, either for anatomical reasons or to practice surgery for human subjects.

Leonardo da Vinci is among those people who cut cadavers and animals alike so he could feverishly draw them and write about them in the 15th and 16th centuries.

In the 1660s, Robert Boyle held his “Experiment 41,” demonstrating the reliance of living creatures on air for their survival. Although holding your breath for a minute demonstrates the same thing, Boyle still helped shift the purpose of animal experimentation from largely anatomical to largely scientific in nature.

Then, after a few centuries of determining that animals need air to live, we enter the 20th century where genetic modification and neuroscience started gaining traction.

In the 1920s, frogs were used to determine that neural communication was dependent on frequency of action potentials and not any kind of magnitude.

In the 1960s, David Hubel and Torsten Wiesel discovered a critical period for the development of a lazy eye using a cat.

Then, in 1989, things would really shift for neuroscience with the creation of the first “knockout mouse” by Mario R. Capecchi, Martin Evans and Oliver Smithies.

A knockout mouse is a genetically modified lab mouse in which a specific gene has been inactivated by the introduction of a foreign DNA sequence. This is so useful to scientific experimentation because it allows researchers to change just one variable, and so draw conclusions about how exactly the knocked-out gene functions in regular, or “Wild-Type,” mice.

First, scientists observe the DNA sequence of the gene they want to knock out of a mouse. Then, a new DNA sequence, which is very similar to the original gene and its neighboring sequence, is engineered but changed just enough to make the gene functionally useless.

Then, this new sequence is introduced to embryonic stem cells taken from a mouse blastocyst. Some of the stem cells will incorporate the new sequence instead of the original gene.

There’s more to it, and it can be a tricky process, but that is essentially how knockout mice are created. They go on to be born with whatever altered gene expression scientists desire.

“Knockin” mice are what they sound like — instead of the removal of a gene, it’s the addition of one.

Mice are popular in neuroscience because of observed similarities between the mouse brain and the human brain. After all, if we aren’t doing science for ourselves, then what’s the point (sarcasm)?

There is a case for diversifying animal models in neuroscience. One meta-analysis found that 35-40 percent of all research efforts in the field are directed to rodents.

University rodents also tend to be super inbred, thus they lack many kinds of genetic and behavioral diversity.

Some believe reintroducing different species and rodent diversity is the only way to obtain results that are helpful to an equally or more diverse human population.

Regardless, animal models seem to be here to stay and I think it’s important to understand its history to interpret the efficacy of this long-standing tradition in the biological sciences.