Wednesday, August 18, 2004

Gene Therapy With Behavioral Consequences...(?)

...In monkeys, anyway, sort of.  Recently, news@nature.com reported on a study, in which the behavior of monkeys was altered by injecting DNA into their brains.  The original article is available, open access, at PNAS.  The title of the Nature news report got my attention: Gene therapy cures monkeys of laziness.  Did the scientists find a way to alter the genetic makeup of monkeys, such that they were better workers?  Could this work for humans?  Could we actually make people into better workers?  Maybe then we could all get a little injection into our skulls and boost the GDP!  Maybe no child will be left behind, for real.  Just get them all to stand in a line, before they take the SAT or whatever, give them a little needle in the skull, hand out some sharp #2 pencils, and let 'em at it!

It turns out that the title is a bit of an exaggeration.  What the researchers did is not really gene therapy, and it did not cure the monkeys of anything.  This degree of hyperbole is unusual for a journal known more generally for being understated.

Gene therapy cures monkeys of laziness
Published online: 11 August 2004; | doi:10.1038/news040809-10
Helen Pilcher

Switching off key gene turns layabout primates into keen workers.

Procrastinating primates can be turned into workaholics, thanks to gene therapy. The discovery, which sheds light on the workings of the brain's reward centre, may further our understanding of mood disorders, such as depression and obsessive-compulsive disorder.

Like many humans, monkeys tend to slack off when their goal is distant, then work harder as a deadline looms. But when a key gene is turned off, the primates work hard from the word go, researchers report in PNAS Online1.

"The gene knockdown triggered a remarkable transformation in the simian work ethic," says Barry Richmond of the National Institute of Mental Health in Bethesda, Maryland, who studied the animals. [...]

The scientists set up a study in which monkeys had to perform a boring, repetitive task.  During the task, the monkeys could see an indicator that showed how long they had to keep going before they would get a reward.   The system monitored how often the monkeys made errors.  It turns out that they make a lot of errors when the reward was a long way off.  As the time for the reward got closer, they started to pay more attention, and made fewer errors. 

Then, they took some monkeys and injected a specially-prepared DNA solution into their brains.  The DNA was an antisense analogue of the region that codes for one kind of dopamine receptor.  The injected DNA would bind to the DNA in the nuclei of the monkeys' brain cells, preventing it from functioning.  This effectively stopped the production of D2 receptors, thereby decreasing the number of such receptors in the brain. 

It turns out that monkeys treated in this way make fewer errors during the early part of the test, when the reward is still a long way off. 

Now, what they did to the monkeys is not really "gene therapy."  They did not insert new genetic material into the functioning nuclei of the monkeys.  They used a nonfunctioning kind of DNA to turn off (temporarily) a normal gene that had been functioning properly.  Furthermore, the treatment did not cure anything.  All it did was to make the monkeys more able to tolerate boredom. 

Ok, so they exaggerated.  Still, is there any chance that this kind of thing could be beneficial for people?  I mean, if you could somehow get past the obvious ethical issues, could we make people better workers? 

First, we can't  get past the ethical issues.  Gene therapy is risky, and could be justified only for treatment of a life-threatening condition.  Also, we already have a way to block D2 receptors without putting a needle inside the skull.  Antipsychotic medications block D2 receptors.  So it turns out that the research cited above really has no hope of ever evolving directly into anything of clinical utility.  It could be important, it that it could help us to develop a better understanding of the connection between genetic constitution and behavior.  Or perhaps it could lead to new targets for drug development.  But something like that would take at least a few decades. 

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