Stephen Strauss, Science Reporter
The Globe and Mail, 1999
Every schoolchild can recite the biological mantra: Living creatures are the fruits of nature and nurture, nurture and nature. Everyone, that is, but the heretical University of Alberta professor Douglas Wahlsten. After more than two decades of studying how the brains of mice form and malform, he believes he has come onto something so startling it does not fit in with any current theory.
'Dramatic physical change is sometimes the result of a biological third way that is neither nature or nurture,' Prof Wahlsten said. 'I think there are very small differences between what are supposed to be genetically identical embryos, things even as seemingly trivial as which cell is next to which cell,' he said. "Most of the time this doesn't matter, but sometimes this can lead to big differences later in life.
If he is right, the third way may explain why one identical twin is left-handed and another right handed, or why some get cleft palates and their brothers and sisters don't. It might also make clear how a person who genetically should be a boy has all the appearances of a girl. More grandly, it holds out the possibility of explaining two of the basic mysteries in developmental biology: How do new complex organs come into being and how do new species evolve?
What professor Wahlsten calls the 'third force' grows literally out of the brains of mice. It has been known for more than fifty years that newborns of some varieties of mice completely lack the corpus callosum, the bundle of nerve fibres that carries information between the two halves of all mammals brains with the exception of marsupials. An identical twin, born in the same womb, will have a fully developed corpus callosum.
The physical formation of what Prof. Wahlsten describes as the 'big brain telephone cable' has recently become an area of intense research in humans. Various studies have correlated differences between men and women and hmosexual and heterosexual men to variations in the size of their respective corpus collosums. humans who also lack a corpus callosum have to overcome a variety of co-ordination problems.This was scientifically alluring, as people without the information bridge seem to function relatively normally.
Does environment or heredity make or break the corpus callosum? The answer seemed to be 'neither'. "It was literally like a coin flip," Prof Wahlsten said. To argue that neither environment nor heredity determined the fate of his almost brainless mice, Prof. Wahlsten had to come up with negative proof (falsification). He checked for a classical pattern of inheritance in any of the mice species but found nothing.Mice without the information bridge were just as likely to produce normal offspring as those with the corpus callosum. He looked at environmental influences in the womb, differences on placement in the uterus (packed close or far away) and the sex of the womb mates. Was the death of a sibling or the health at birth a predictor? Were womb mates alike because of some environmental explanation?
'To make a long story short, nothing correlates,' he said. So he tried to give mice fetuses an environmental kick, starving pregnant mothers, feeding others on alcohol and transplanting ovaries between varieties. Still nothing.
Finally, he looked at what occurred when the corpus callosum formed or failed to form. Nothing showed for the first 14 days of the gestation cycle. Then small variations in the timing of the brain formation took on a gigantic importance. The corpus callosum tissue in both hemispheres headed toward one another.If underlying tissue connecting the hemispheres arrived at the juncture a bit before or afterward, the brain's telephone cable crossed over. If the tissue bridge cells were hours late in arriving, the entire corpus callosum didn't form.
'It's a threshold situation, timing is everything,' Prof Wahlsten said. But what the nerves did when they couldn't meet was almost as interesting. 'If they didn't get across,' he said, 'they turned back and began to follow unusual pathways. 'It was almost like exploring alternative possibilities,' he said and explained why open-ended exploration may be significant. 'This could be something which could be important for evolution and explain things like how you may get new structures in the brain.'
Professor Wahlsten's championing of chance biology excites other researchers who find themselves facing other conditions that defie environmental or hereditary explanations. Fred Biddle, a medical geneticist at the University of Calgary, has been looking at cleft lip, handedness in identical mice and conditions in which individuals are genetically male but look like female. In each of these cases, he believes, what determines a condition is the biological third way. In Prof Biddle's eyes, the hardest thing about the developmental abnormalities are not their obvious unpredictability, but getting people to accept the role of chance in biology.
'One of my students said it clearly: "Why didn't the textbook tell us that," she asked, and i just had to tell her that the explanation is just unfolding now,' Prof Biddle said, 'Doug is right at the edge - and I don't mean that in a bad way.'
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