Tuesday, September 26, 2006

The Male Brain (of Mice and Men)

We recently wrote about how neuroscience is a burgeoning field; some say that it will displace genetics as the leading edge of scientific discoveries in the 21st century. Significant ethical issues come along with discoveries about how our brains work.

Fortunately, thanks to the vision and generosity of Paul Allen, scientific researchers will now have the tools they need to unlock the brain's mysteries. From today's Seattle Times:
The type of brain map that used to grace high-school biology texts looked like a quilt: A pink chunk labeled "vision" bumped up against a blue blob that was the seat of language and a yellow swath representing motor perception.

Those crude representations were the result of centuries' worth of painstaking dissection, coupled with case studies of people suffering from brain damage and disease.

It took only three years for a Seattle lab founded by Microsoft mogul and philanthropist Paul Allen to revolutionize the landscape of neuroscience by creating a map of the brain that goes far beyond topography to pinpoint the workings of individual cells.

Allen, who donated $100 million to the lab, said he is so pleased with the results that he will consider similar, large-scale science projects in the future.

"This was a great opportunity to do something here that made a difference, and that we could do quickly," he said. "We'll certainly look for more opportunities like this."

Experts say the Allen Brain Atlas, which will be formally unveiled today, will boost understanding of brain circuits and chemistry — and what goes wrong in conditions ranging from schizophrenia and autism to Parkinson's disease and drug addiction.

The initial mapping will be done on male mice. While we applaud their efforts, it is important not to assume discoveries based on male models (mice or men) can be directly translated to the female gender.

We found this out with heart disease. Paul: Remember the ladies!


BuddhistValkyrie said...

I understand why they don't test as much as they should on women (understand, don't agree), but you say that the initial mapping will be done on male mice - plural. Is there a specific reason they're limiting it to male mice? (Is this an implicit acknowledgement that they expect to find differences, and are tackling the sexes separately?)

Kathryn Hinsch said...

Great question - and while it is difficult to have an exact scientific discussion via blog, I'd thought I'd share with readers the answer I received about "why male mice" from a scientist involved with the effort:

You cannot analyze all 20,000 genes on one mouse's brain - they had to use ~8,000 mouse brains. Therefore it's important to minimize variability between the mice. To do this in females, it would require a) synchronizing all the mice at exactly the same phase in their estrous cycle (which would in turn require taking blood samples from each mouse and measuring hormone levels by RIA, before sacrificing the mice for analysis); b) taking multiple time points throughout the estrous cycle, to see whether and if the expression of any genes changes. This is an interesting question, but would have expanded the scale of the entire project by a factor of 3-5, and that would have been impossible given the aggressive time-frame.

This is also the reason that most mouse/rat behavioral experiments are performed on males. In any behavioral experiment, even with genetically identical inbred mouse strains, there are so many uncontrolled variables (early life history, time from last meal, amount of sleep, "phase of the moon") that the only way to get reproducible results is to minimize all the controllable sources of variability. Not having to deal with the variability in hormone levels -- not "fluctuations," which implies random changes within an individual, but even predictable, cyclical changes whose exact phases may nevertheless vary from individual to individual within a population -- is another important variable to get under control and easiest to do by sticking with males.

That said, it would be interesting to investigate gender dimorphic differences in gene expression, under conditions where hormonal levels could be measured and held constant between individuals.

Thanks to Dr. David J. Anderson, Cal. Tech.

Emilie Clemmens said...

Two thoughts: both on quotes from the Seattle Times article on this exciting development.

Scientists were surprised to discover that 80 percent of all mouse genes are switched on somewhere in the brain, Jones said.

"We think there are probably more cell types within the brain than in all the other organs of the body combined," he said.

WOW! 80%! That is truly remarkable. And more cell types than all other organs combined? That information alone is astounding and exciting to ponder.

The next:

The federal government would have been reluctant to fund a project on such a scale, said Dr. Thomas Insel, director of the National Institute of Mental Health.

"For a private donor to build this kind of a spectacular electronic atlas and just say to the world: 'Have at it' — I can't think of a precedent for that," he said.

This immediately made me think of Bill Gates and what he's doing with global health. Is this the new economy? Do we need to hope for and rely on the altruism of the very wealthy to make major advances in science and public health?

BuddhistValkyrie said...

Kathryn: Thanks so much for the information. That does make a lot of sense, although I do hope that Dr. Anderson and team do revisit this with female mice. Obviously more of a pain to control, but it seems like, since there are so many variables that could change and influence the mapping, it almost must be done.