August 11, 2004
Monkeys Turned Into Workaholics With Brain Gene Suppression

The future is going to be a very different place. We live on the verge of an age of genetically engineered emotion and motivation alteration.

Using a new molecular genetic technique, scientists have turned procrastinating primates into workaholics by temporarily suppressing a gene in a brain circuit involved in reward learning. Without the gene, the monkeys lost their sense of balance between reward and the work required to get it, say researchers at the NIH's National Institute of Mental Health (NIMH).

"The gene makes a receptor for a key brain messenger chemical, dopamine," explained Barry Richmond, M.D., NIMH Laboratory of Neuropsychology. "The gene knockdown triggered a remarkable transformation in the simian work ethic. Like many of us, monkeys normally slack off initially in working toward a distant goal. They work more efficiently make fewer errors as they get closer to being rewarded. But without the dopamine receptor, they consistently stayed on-task and made few errors, because they could no longer learn to use visual cues to predict how their work was going to get them a reward."

Richmond, Zheng Liu, Ph.D., Edward Ginns, M.D., and colleagues, report on their findings in the August 17, 2004 Proceedings of the National Academy of Sciences, published online the week of August 9th.

Richmond's team trained monkeys to release a lever when a spot on a computer screen turned from red to green. The animals knew they had performed the task correctly when the spot turned blue. A visual cue--a gray bar on the screen--got brighter as they progressed through a succession of trials required to get a juice treat. Though never punished, the monkeys couldn't graduate to the next level until they had successfully completed the current trial.

As in a previous study using the same task, the monkeys made progressively fewer errors with each trial as the reward approached, with the fewest occurring during the rewarded trial. Previous studies had also traced the monkeys' ability to associate the visual cues with the reward to the rhinal cortex, which is rich in dopamine. There was also reason to suspect that the dopamine D2 receptor in this area might be critical for reward learning. To find out, the researchers needed a way to temporarily knock it out of action.

They used DNA antisense oligonucleotides which are short stretches of DNA sequence which match with a target gene to bind to it to prevent ts expression.

Molecular geneticist Ginns, who recently moved from NIMH to the University of Massachusetts, adapted an approach originally used in mice. He fashioned an agent (DNA antisense expression construct) that, when injected directly into the rhinal cortex of four trained monkeys, spawned a kind of decoy molecule which tricked cells there into turning-off D2 expression for several weeks. This depleted the area of D2 receptors, impairing the monkeys' reward learning. For a few months, the monkeys were unable to associate the visual cues with the workload to learn how many trials needed to be completed to get the reward.

Monkeys are usually procrastinators. But the lack of D2 receptors turned them into workaholics.

"The monkeys became extreme workaholics, as evidenced by a sustained low rate of errors in performing the experimental task, irrespective of how distant the reward might be," said Richmond. "This was conspicuously out-of-character for these animals. Like people, they tend to procrastinate when they know they will have to do more work before getting a reward."

Using the same technique to turn off NMDA receptors did to increase motive to work for a reward.

To make sure that it was, indeed, the lack of D2 receptors that was causing the observed effect, the researchers played a similar recombinant decoy trick targeted at the gene that codes for receptors for another neurotransmitter abundant in the rhinal cortex: NMDA (N-methlD-aspartate). Three monkeys lacking the NMDA receptor in the rhinal cortex showed no impairment in reward learning, confirming that the D2 receptor is critical for learning that cues are related to reward prediction. The researchers also confirmed that the DNA treatments actually affected the targeted receptors by measuring receptor binding following the intervention in two other monkeys' brains.

And you can bet these researchers are thinking about how to use this technique on people.

"This new technique permits researchers to, in effect, measure the effects of a long-term, yet reversible, lesion of a single molecular mechanism," said Richmond. "This could lead to important discoveries that impact public health. In this case, it's worth noting that the ability to associate work with reward is disturbed in mental disorders, including schizophrenia, mood disorders and obsessive-compulsive disorder, so our finding of the pivotal role played by this gene and circuit may be of clinical interest," suggested Richmond.

"For example, people who are depressed often feel nothing is worth the work. People with OCD work incessantly; even when they get rewarded they feel they must repeat the task. In mania, people will work feverishly for rewards that aren't worth the trouble to most of us."

Of course there is the classical science fiction threat of companies or governments taking over the minds of people to train them to work hard for the organization. The classical abuses will probably happen eventually and may lead to some pretty horrible outcomes. But I can easily imagine why lots of people (FuturePundit included) will choose to use drugs to motivate themselves. Looking at a big long work task? Know that you are hurting yourself by not working harder during the earlier stages? Well, take some DNA antisense drug and as your D2 receptor concentration drops you may find yourself working harder for distant rewards.

The problems with delivering DNA antisense oligonucleotides into cells will be solved in time as part of the larger push to develop techniques to deliver gene therapy into cells. Once the delivery vehicles are available the use of gene therapy will allowing temporary and permanent modification of personality, emotional state, and behavior on a scale that will make Prozac and Zoloft seem like primitive tools in comparison.

Update: And what about the economic impact of motivation enhancing gene therapy? While I'm bearish about the next 20 or 30 years due to aging populations and other demographic problems once we can raise IQ, increase motivation, and do other cognitive tweaking it is hard to see how economic output will not be greatly increased. Raising IQ is going to be harder to do than motivation alteration. But just reducing the amount of procrastination would be a big boost to productivity. Add in rejuvenation therapies, IQ enhancement of progeny (which will be easier to do than IQ enhancement of adutls), and even cognitive enhancement of adults and in a longer time frame the human part of the economic productivity equation looks much rosier. What is harder to predict is just when these various capabilities will be available.

Update II: Note that the level of motivation varies greatly from one person to the next. Also, some people are better set up to pursue longer term goals and others need more immediate rewards to get off their duffs and do anything. This latest result suggests a possible reason: differing levels of expression of genes that control dopamine D2 receptor concentrations. Once offspring genetic engineering becomes possible will people opt to have children who are more motivated than they are? Also, will employers surreptitiously take samples of DNA from job applicants to decide which applicants will be the hardest workers? Will some applicants even go so far as to state that while their natural DNA sequences tend to make them slackers and procrastinators they have permanently altered their personalities to turn themselves into workaholic maniacs? Will applicants even supply suitably certified medical records as evidence of their altered state? It all seems very plausible to me...

Share |      Randall Parker, 2004 August 11 11:57 AM  Brain Emotion Alteration

Brock said at August 11, 2004 5:46 PM:

If people are less sensitive to rewards, will they pursue fruitless endeavors for longer periods of time, wasting more resources on them? Sometimes the most efficient actor is the one who knows to stop throwing good money after bad.

Not trying to rain on this cloud, an I would _love_ this to work as Futurepundit theorizes, but I'll wait until we see how good people are at judging rewards more complicated than a juice squirt.

gmoke said at August 11, 2004 8:03 PM:

Now this is something that may definitely be on the political radar for the next couple of generations.

Carina said at August 12, 2004 5:57 AM:

I, too, would consider trying such a drug, were it available commercially. Its nearest known approximations, Ritalin and Adderall, are heavily regulated as it is. I expect DNA antisense would be similarly restricted to those with medically "proven" need for the forseeable future.

Russell said at August 12, 2004 7:01 AM:

I work in a courtroom and I can very easily see a judge requiring a criminal who is habitually out of work to get on a medication like this. Doesn't it seem more likely that a drug will come out that mimics the gene (or squashes it) than gene therapy?

Steve Sailer said at August 12, 2004 12:21 PM:

Personally, I _don't_ want to work harder. I want to be able to buy a troop of genetically enhanced hard working monkeys to do my drudge work for me.

Rene said at August 12, 2004 4:24 PM:

This is clearly an american idea. My cousins back in Europe would laugh at the thought of a drug to enhance productivity. The main challenge in Europe is finding more ways to reduce productivity, not enhance it.
I would worry about giving this type of drug to a criminal mind, considering the type of work a criminal mind is prone to dwell on.
The subtlety of this approach is encouraging. Clearly the tools for doing neuroscience research are improving.

Grady said at August 13, 2004 9:27 AM:

There's a whole lot of begging of the question being done here.

The research did not prove that the motivation of the monkeys was increased. It decoupled their effort/reward awareness by knocking out their ability to anticipate the coming reward. An increase in motivation is just one possible interpretation. It could just as easily have been because the animals ability to look into the future or plan was impaired. You don't want to lose the ability to anticipate things, because it's as likely to be an impending disaster as an impending reward.

The paper is more interesting as a technical demonstration of reducing function in a specific brain region than for the behavioral effects they noticed. Though the effects are interesting, they're so open to interpretation that all this pondering about whether in the future we'll be required to have something like this done is on the same level with wondering if we will all be forced to have lobotomies because people who have them typically don't engage in criminal behavior.

Bob said at August 13, 2004 1:10 PM:

Oh Great! Let's think about this for a moment. If this 'motivation' gene therapy turns out to not be 'personification' on the part of the researchers, and adapting from an old Austrian Officer's Manual: Smart Energetic People get the most done, Stupid Lazy People get the least done but don't cause any harm, Smart Lazy People at least keep out of the way, and Stupid Energetic People cause the most damage. Now we're talking about the possibility of only having Smart Energetics and Stupid Energetics. It's been my experience that Stupid Energetics do far more damage than Smart Energetics do good. So....We're freakin' doomed.

Lazy Bones said at August 13, 2004 3:58 PM:

Oh joy, now all we need is for someone to find a way to negate our need to sleep and we'll be all set to work 24/7 with just enough time in each day to quickly shower, change clothes, and eat. Sounds swell.

noone said at August 14, 2004 2:28 PM:

If your employer starts offering free lunches,decline.


And polish up that resume.

Rene said at August 15, 2004 5:44 PM:

You guys must be wage slaves. That's so passe'.

When you're both boss and employee, you start to value productivity a lot more than if you're a peon wage slave working for somebody else.
You may as well belong to a union. Sheeesh!

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