Prickly challenges of breakthrough fetal brain research: Learning about human differences

Our brains express more of our genes than any other organ does. One estimate claims the human brain uses 85 percent of its genes at one time or another throughout life.

This brain work is still mostly a mystery, and no stage of life has been more mysterious than what goes on in our brains before birth. But there’s a research project that has begun to give us a peek at brain gene activity during fetal life, when our brains are first developing. It’s the BrainSpan Atlas of the Developing Human Brain, which aims to profile gene activity throughout the course of brain development.

One thing it has told us already, says Tom Insel, is that the fetal brain is profoundly different from the adult brain. Insel heads the National Institute of Mental Health, the government agency supporting the BrainSpan project. “In fact, so many genes are translated differently in the fetal brain, the fetal brain at a molecular level could almost be considered a different organ.”

During fetal life, 80 percent of the genes expressed in the brain showed a pattern of expression different from that seen after birth. Many genes are spliced in novel ways during fetal development, and they produce unique protein variants. “Some of the genetic signals associated with mental disorders, which previously were difficult to understand, appear in those regions that are relevant in fetal brain development but perhaps not thereafter,” Insel says.

First BrainSpan findings

Researchers at the Allen Institute for Brain Science in Seattle released the first fetal brain map in April. It reveals when and where genes are turned on at two times a few weeks apart in the middle trimester of gestation. Greg Miller described some of the findings at Wired.

“For example, 34 genes whose sequences differ in interesting ways between humans and other primates appeared to be especially active in the developing frontal cortex. This is a region that’s relatively large in humans and thought to be especially important for social behavior, planning for the future, and other cognitive skills that humans excel at compared to many other species.”

Which is, I guess, exactly what we would expect.

The BrainSpan findings are being fed into an open-access database that has already advanced knowledge about autism and schizophrenia in two papers published last year. When researchers examined genes that have been associated with autism in previous studies, and which don’t seem to be functionally related in the adult brain, they found that the genes were active at the same time in the same cells in one layer of the developing fetal cortex. A study involving genes associated with schizophrenia identified a similar network of coordinated gene expression in the developing fetal brain.

If you hate Big Government, you’ll hate this research. We have the Great Recession to thank for it. The BrainSpan Atlas of the Developing Human Brain is funded by the National Institute of Mental Health through the 2009 American Recovery and Reinvestment Act (ARRA, aka the stimulus package.)

The limits of fetal brain gene research 

These BrainSpan studies were done on tens of thousands of brain tissue samples so small that they had to be cut out with a laser. The samples came from brains taken from preterm stillbirths in the middle of gestation, two at 15-16 weeks and two at 21 weeks.

Although this is a critical point in gestation when the cerebral cortex is developing, it’s possible–probable, even–that a lot of the things we would like to know about the developing brain happen earlier, much earlier. Also later. Also, this was only four brains. Studying them is a brilliant achievement, but we don’t at this stage know whether the picture they are giving us reflects what typically goes on in all fetal lives.

Virginia Hughes has a helpful piece in National Geographic explaining (1) Why it’s so important to study human brain tissue itself (including human fetal brain tissue) rather than relying on studies in mice or other animals; and (2) Why studying those tissues, which may well be altered by the process of acquiring them and preserving them, should be accepted with a grain of salt; and (3) Why brain tissues from just one or even a few fetuses may not represent the range of possibilities accurately.

This carping does not mean I’m not in awe of the technical accomplishments, the imagination, and the useful tools this freely available project provides for researchers today and for years to come. Who can be anything but heartened at having new reasons to hope for reducing the toll of schizophrenia and autism? And, in time, other dreaded conditions that begin in the brain long before birth?

But of course it’s impossible not to wonder where else this work is leading us. Will learning more about the fetal brain generate more ways of tinkering with it? Eliminating undesirable traits, for instance? Tweaking fetal brain genes to improve math ability or musical talent? And intelligence, of course? ART–assisted reproductive technology–is already a hugely popular commercial enterprise attuned to the desires of its customers. If and when these kinds of choices exist, you can bet they will be used. If you could afford it, would you give up a chance to make your kid smarter? I wouldn’t.

Not that these are new vexations. Concerns about the coming possibilities for choosing children’s traits have been muttered over and worried about for a very long time, although they have come to no resolution. Despite several government commissions and private scholarly bioethical meditations, we’ve made next to no progress in figuring out how to handle such seemingly inevitable trends.

It’s out of the question–and also not possible–to control research and deprive ourselves of its undoubted benefits, not to mention the unanticipated discoveries that will doubtless ensue. Even if we could figure out ways to obtain the good stuff from research and avoid the bad, how would we define the bad? Who decides? In some places in the world that might be possible, places where the rules for good and bad are handed down from on high. But I don’t want to live in those places, and neither do you. So here we are, still at that impasse. Letting things play out. Hoping for the best.

Tabitha M. Powledge is a long-time science journalist and a contributing columnist for the Genetic Literacy Project. She writes On Science Blogs for the PLOS Blogs Network. New posts on Fridays.

 

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