Biologist recognizes junior paper on brain anatomy as a natural for Nature
Princeton NJ -- Damon Clark is ready to graduate. So why, with his senior thesis behind him and his last exam finished, is he still working with biologist Sam Wang on his junior paper?
Now, as Clark prepares to leave for a one-year stint doing refugee work in Somaliland under the Princeton-in-Africa program, he and Wang are still working together, preparing responses to questions from other scientists from around the world.
"I didn't expect it to go on this long," laughs Clark. "It's probably the longest JP around."
Analyzing the brain
Clark's research focused on comparative brain anatomy. Working with Bell Labs scientist Partha Mitra, Clark and Wang devised a simple but powerful method for analyzing brain anatomy, providing the first reliable measure of how brains of humans and other mammals are related to one another across evolution.
In their Nature paper, the researchers show how comparing the relative sizes of 11 brain parts reveals a unique brain structure for each species. They calculated the percentage of total brain volume contributed by each part and created the term "cerebrotype" to describe the resulting 11-number characterization, just as the word "genotype" describes the unique DNA sequence for each species.
The analysis shows that mammals fall into a spectrum of cerebrotypes, with humans at one end and insect-eaters, such as hedgehogs, at the other.
"Intuitively, we know there is something about our brains that is extreme," said Wang. "What we have here is a direct measure of one way in which our brains are extreme."
For Clark, the experience provided a unique insight into how scientific advances are made and how peer-reviewed papers are published. "It was really good to see the actual scientific process, which you don't normally see as an undergraduate," he said.
When Wang proposed carrying on with the junior paper research and trying to develop it into an article for publication, he warned Clark that it would be a lot of work. Clark thought Wang was exaggerating. "Sam said it would be about the same amount of work as I first put into it, once over," said Clark. "It wound up being about the same work twice over."
By that time, Clark had his senior thesis to think about. "It was a consideration, because I had to get my thesis done," he said. "But getting a paper published is really worthwhile, and it really expanded my ideas about what I will do in graduate school. And it cemented the idea that I wanted to go to graduate school."
After returning from Somaliland, Clark will pursue a Ph.D. in physics at Harvard University.
As a physics major, Clark was doing his junior paper in molecular biology to fulfill the requirements for an interdisciplinary certificate in biophysics. The research originally focused on finding mathematical patterns behind certain trends in the way brains change with the sizes of animals.
"We were looking for underlying engineering or design principles that might account for how evolution led to one brain architecture and not another," said Mitra.
As the work evolved, Clark needed a considerable amount of data about actual brains. Fortunately, he did not have to do any dissecting himself; he worked with a 20-year-old database assembled by European researchers who cataloged information about the brains of 300 animals.
In the end, the research may help scientists understand the selective forces that drove the evolution of humans and other animals. Brain areas that showed the most growth over the course of evolution are likely to perform functions that conferred a selective advantage, said Wang.
The research confirmed, for example, previous studies showing that one brain area, the neocortex, grew rapidly over the course of evolution, ranging from 16 percent of the brain in insect-eaters to 80 percent in humans. The neocortex is responsible for social interactions, reasoning and other complex cognitive tasks, suggesting that the outcome of social interactions has been a powerful evolutionary force. Interestingly, even when Wang and colleagues eliminated the neocortex from their analysis, humans still had a unique brain structure, appearing on the extreme end of the chart.
In general, the researchers found that animals with the most similar cerebrotypes were also the most closely related by evolution. Within groups of related species, total brain size varied by as much as 100-fold, but the relative sizes of their brain parts -- their cerebrotypes -- remained relatively constant. Shifts in cerebrotype occurred with the emergence of new groups, such as the evolution of older monkeys into the great apes into human-like primates.
Another implication of the research is that the genetic mechanisms that control the development of the brain's structure may be much simpler than previously thought. Wang speculates that many differences between the brains of humans and those of the simplest mammals may result from evolutionary pressures on just a few genes.
The reason is that, as evolution progressed, the relative sizes of the 11 brain areas shifted in only limited ways. If there were hundreds of genes independently controlling the sizes of the brain areas, then there would be a great diversity of cerebrotypes among mammals -- much more than what the researchers found. Instead, they were able to reduce the many variations between the 11 brain areas to a relatively simple, two-dimensional diagram.
Previous brain-comparison studies had focused on either the whole brain or did not compare brain regions directly with each other. Some, for example, measured the relationship of overall brain size to body size and compared that measure among species of different body weights. That analysis yielded inconclusive results, suggesting that human brains were most closely related to those of spider monkeys, which are not considered to be close evolutionary relatives. However, the researchers' new results follow widely accepted evolutionary charts: mammals that are closely related by evolution also proved to have similar cerebrotypes.
"It provides a little insight into who we are and how we got here," said Wang.
After Clark leaves Princeton, another undergraduate
student in Wang's laboratory, Mark Burish, is continuing the
research for his senior thesis, applying cerebrotype
analysis into birds, fish and lizards. As for Clark, he also
may return to the subject; although he had not considered it
before, he is now planning to take up neuroscience research
in graduate school, with one major publication in the field
already to his name.