September 14, 2006
Gene Knock-Out Makes Happy Mice

Some people spend their whole lives in search of happiness and escape from a feeling of hopelessness and ennui. They lack the technology that would grant them immediate satisfaction. Knock out a gene and be happy.

A new breed of permanently 'cheerful' mouse is providing hope of a new treatment for clinical depression. TREK-1 is a gene that can affect transmission of serotonin in the brain. Serotonin is known to play an important role in mood, sleep and sexuality. By breeding mice with an absence of TREK-1, researchers were able create a depression-resistant strain. The details of this research, which involved an international collaboration with scientists from the University of Nice, France, are published in Nature Neuroscience this week.

"Depression is a devastating illness, which affects around 10 percent of people at some point in their life," says Dr. Guy Debonnel an MUHC psychiatrist, professor in the Department of Psychiatry at McGill University, and principal author of the new research. "Current medications for clinical depression are ineffective for a third of patients, which is why the development of alternate treatments is so important."

Mice without the TREK-1 gene ("knock-out" mice) were created and bred in collaboration with Dr. Michel Lazdunski, co-author of the research, in his laboratory at the University of Nice, France. "These 'knock-out' mice were then tested using separate behavioral, electrophysiological and biochemical measures known to gauge 'depression' in animals," says Dr. Debonnel. "The results really surprised us; our 'knock-out' mice acted as if they had been treated with antidepressants for at least three weeks."

One of the reasons I watch for mouse gene knock-out studies is that they are a glimpse into the choices prospective parents (and domineering governments) will face when it becomes possible to tinker with the DNA of eggs, sperm, and embryos. In the future some people will opt for offspring genetic engineering to make their kids congenitally happy uncurable optimists. Other people will genetically engineer their kids to be highly objective analytical realists. Not a few of the latter will want to come up with ways to infect the obnoxiously optimistic with viruses that will reprogram them for more realism and less optimism.

Other future parents will opt for drugs instead of genetic engineering to make their kids happy, calm, content, and confident. Make Johnny and Jill grow up as joyful kids but then tell them at age 18 they just have to stop taking the pills and they'll be able to suffer all the doubts, depression, and sadness that the older generations experienced.

Gene knock-out studies also provide glimpses into just how little free will we have (if we even have any at all).

The discoveries from gene knock-out studies will become a torrent when efforts to create mice with gene knock-outs for each mouse gene achieve their goals.

Share |      Randall Parker, 2006 September 14 12:10 AM  Brain Genetics

michael vassar said at September 14, 2006 7:26 AM:

You know Randall, the conceptual problems with free will are so utterly profound that there really isn't any possible evidence that could contribute to further discrediting it. Free will simply isn't a scientific hypothesis. Predicting novel phenomena is precisely what it *doesn't* attempt to do. What it is is a name for a subjective experience that we all have, and which doesn't go away in the face of logical contradiction.

Mike Long said at September 14, 2006 1:01 PM:

"congenitally happy uncurable optimists"

- Like Aubrey De Grey and the rest of the SENS promoters?

hibbs02 said at September 15, 2006 8:31 AM:

I was talking to someone about the current state of research in the field of genetics and that was precisely the phrase I used, "The more I read about genes and their influences, I have to wonder just how much free will we humans have."

Let's leave aside things like congental illnesses which can limit our physical/mental abilities. Such conditions are obvious and already considered in our social policy. Let's look deeper into the growing state of knowledge we have of genetics and its influences.

I think it is beyond argument that a person's genetics provide major influence on whether a person is an alcoholic, drug abuser, overweight, level of motivation to work/study/learn, temperment, sexual orientation, happiness level, talents (such as artistic such as painting/music, math, reading emotions of others, etc).

Genes are primarily responsible for a person's intelligence which when combined with a person's energy level/motivation gives a fairly precise prediction of exactly how successful the person will be in an open society such as America's.

It is certainly arguable that our genes influence our political persuasion and religious affiliation and a host of other more intangible attributes.

And on and on. . .

When you add environment into the mix where a child who cannot be considered to be responsible is subject to everything from abuse to indoctrination. . .

Well, not only do I have to wonder just how much free will we have but more and more I understand the saying, "There but for the grace of God go I."

Further, I am moving further from a conservative leaning libertarian into a nebulous region where I have to wonder what is the correct course for various social policies. Welfare as we knew it was a disaster, it contributed (or perhaps more strongly caused) poverty and untold amounts of pain for children when there were disincentives to work or marry. But, then again. . .

I would bet money there are people who are essentially disabled in a non obvious way. They just got screwed by the luck of the draw. Low IQ, but not low enough to be considered developmentally disabled. Low motivation. A very strong tendency toward being sedentary. (Which is fine if you get the hand with high IQ and mathmatical/computer talents where the desire to sit without moving fits perfectly with your programming in a cubicle job but starts to screw you when your only employment option is manual labor.) Anti-social tendencies combined with poor childhood socialization. Heavy depression that destroys all hope on top of an early childhood environment of abuse which instilled serious levels of anger and hatred of authority.

Add on top of all this a tendency to be very overweight exacerbated by the sedentary tendencies. Put in a helping of butt ugly.

Add in whatever you want to mix, there are lots more negative traits that it is becoming clearer and clearer that our genes determine. . .

Is this poor person (and I'm betting there are lots of them in our population pool) really responsible for being unemployable? How do we as a society address this as the science becomes clearer but the ability to fix it isn't around yet?

I'm all about taking responsibility for your life but this hypothetical guy/gal doesn't have the tools. They been screwed by the genetic lottery as much as a mentally retarded quadraplegic, it just isn't obvious.

Conversely, if you were born smart, handsome, gregarious and happy (all four of these traits almost solely from genes) into a middle class or higher family to good parents that loved you and were able to help you and guide you. . .well, just how much of your success are your REALLY responsible for Mr./Ms. I'm the captain of my fate/those people just need to get their act together like I did?

Randall Parker said at September 18, 2006 5:01 PM:

Mike Long,

What obstacles are there that can not be overcome that could prevent the development of full rejuvenation therapies?

One can debate when full body rejuvenation will become possible. But do you question whether it is possible at all?

I tend toward a more optimistic view on timeline (say 30 years before Actuarial Escape Velocity is achieved) because the rate of advance of biotech is increasingly looking more like the rate of advance of electronic tech. We have patterns of advance in biotech with DNA sequencing, gene array chips, and the like that are like Moore's Law in semiconductors.

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