Harvard Professors Model Intestine Shape

Harvard professors recently determined how vertebrate intestines grow into their characteristically coiled shape, through a combination of biological methods and mathematical modeling.

Researchers began by considering the intestine of the chicken.

For the last 15 years, Cliff Tabin, head of the Department of Genetics at Harvard Medical School, has been investigating the underlying biological causes for the orientation, or chirality, of intestinal looping.

But, while trying to understand how a chicken’s intestine grows, Tabin, a biologist, turned to friend and Harvard mathematician Lakshminarayanan Mahadevan for help.

Mahadevan realized that physics could be used to explain the looping: each loop does not have to be formed separately, but rather, if the conditions are right, all the loops will form naturally as a consequence of basic physics laws.

It came down to a simple matter of stress and strain on parts of the chicken’s intestine, producing its coiled shape.

Mahadevan’s mathematical model proved accurate when tested. Not only could it predict the thickness and shape of chicken intestines, but with the proper experimentally-determined inputs, it could also predict the precise coiling of quail, zebra finch, and mouse intestines as well.

Mahadevan is a professor of mathematics and of organismic and evolutionary biology.

Normally, Tabin employs more biological methods to understand how organs and body parts form. That process is called morphogenesis.

For example, when studying the chicken intestine, his lab considered tell-tale biochemical signs, including the different functions of the cells in the animal’s intestine.

Using this approach, his lab determined which direction the chicken’s intestine normally curls.

“At that point, it was clear that the next stage would be to look at how the individual loops form,” said Tabin.

But that’s when Tabin’s biological methods hit a roadblock.

“We really thought it would be more of the same, but we looked and it wasn’t,” said Tabin.

Tabin said his study of the intestine is part of a larger project to understand left-right asymmetry in vertebrates. In humans, this asymmetry most prominently manifests itself in the positioning of the heart, which rests on the left side of the human body.

While Tabin acknowledged that the research will probably not have any direct effect on society for many decades, he said that there are a number of severe medical conditions associated with malformed organs and that regenerative medicine may someday expand on his and Mahadevan’s work to successfully regrow them.

“Certainly, understanding morphogeneis will be essential for regenerative medicine in the long run,” said Tabin.

—Staff writer Nitish Lakhanpal can be reached at nitishlakhanpal@college.harvard.edu.