The Road to Intelligence - One Mouse at a Time

For many people, the desire to become more intelligent is based on societal and practical reasons. The smarter the individual is, the more likely he will be respected by those around them, provided that a certain level of friendly personality accompanies him. In terms of pragmatism, more intelligence is often related to more level of education, which frequently links itself to higher salaries.

There is also an important need to maintain the certain level of intelligence as individual ages. Despite the countless medical improvements that prolong our life by physical means, the mankind is, in some ways, helpless by neurodegenerative diseases. Intelligence then does not equate to becoming "smarter"; it refers to being able to continue the daily activities.

I Present You... Doogie

About a decade ago in 1999, Princeton neurobiologist Joe Z. Tsien collaborated with his colleagues from MIT and the University of Washington to pursue in the journey to find the way to improve the intelligence. He modified a single gene called NR2B to make a smarter strain of mouse named Doogie. NR2B is a special gene involved in the coding of NMDA receptors. NMDA receptors are one important type of glutamate receptor that specializes in memory and learning. More details about NMDA receptors are available at Biology of the NMDA Receptor, which is free to public, or other books regarding neuroscience or psychology.

Anyway, Tsien showed earlier that restricting the expression of NR2B gene caused impairment of the animal's ability to learn and remember. In this Doogie project, he received assistance from Guosong Liu at MIT, who confirmed that mice with additional NR2B genes did show an increased level of NMDA activity. Now, it was time to test if these transgenic mice were actually smarter than the average mice.

Tsien and his colleagues conducted several experiments to examine recognition and emotional memory. With recognition, they placed both control (the average mice) and modified mice to explore two types of objects for five minutes. Several days later, they replaced one of the objects and put the mice back into the container. They discovered that unlike control mice which spent the same amount of time on each of the object, the modified mice spent more time on the replaced object, indicating that it "remembers" seeing the older object before.

To test emotional memory, both kinds of mice were shocked by a mild stimulus, and were placed back into the chamber one hour, one day, and 10 days later. In these cases, modified mice seemed to show more fears for shock than controlled mice, representing the better level of emotional recall of the initial shocks.¹

So, Now What...

Last year, National Geographic released a recent study featuring Tsien. It discussed another intelligent mouse known as Hobbie-J, whose level of expression of NR2B was also amplified. Unlike the first article in 1999, however, this one also talked about limitations on expanding the research to humans. It explained that one cause is ethical reason, which prevents doing any modification at embryo level and thus, requires use of drugs instead. Another worry is that too much memory can be a negative thing. It's like imaging that you remember every little positive and every little negative event that ever happened to you. The article does hint, however, a possibility to curing mental problems like Alzheimer's disease.²

Going From Rat to Human Is Then...

Even with the previous article, it seems unclear to me whether such task - the idea of producing drug that can genetically amplify the level of expression of NR2B - is an easy task. Synthesizing drug is difficult because in order for something foreign to come into the brain, it needs to be encapsulated, protected from antibodies. Furthermore, even if we are able to synthesize such drug, there is a need for testing the safety of drugs for other parts of the brain and the body, and as with anything in healthcare, it would be a while before cost can be reduced. This does not mean that those researches are not valuable though. It just means that we have a long way to go still.

Works Cited

¹ Kristin Leutwyler, "Making Smart Mice," Scientific American 7 Sept. 1999.

² Matt Kaplan, "Rat Made Supersmart - Similar Boost Unsafe in Humans?" National Geographic 12 Nov. 2009, http://news.nationalgeographic.com/news/2009/11/091112-smartest-rat-memory.html