Tuesday, August 11, 2015

Our appendix: expendable no more. An allegory that scientific ideas reflect the culture* of their times.

Textbooks teach us our appendix is a vestigial organ. Charles Darwin (1871, The Descent of Man and Selection in Relation to Sex) concluded that our appendix must be an evolutionary remnant from a primate ancestor that ate leaves.

I never thought to question received wisdom about our appendix until 2007 when I read a Journal of Theoretical Biology in-press article Biofilms in the large bowel suggest an apparent function of the human vermiform appendix proposing that our appendix is not vestigial but has an important immune function in maintaining symbiotic gut bacteria. Let's systematically consider what William Parker and colleagues at the Duke University Medical Center in Durham, North Carolina propose and how our appendix could function immunologically.


Our appendix has a narrow lumen and is located at the lower end of the cecum. As Bollinger et al's figure above shows, anatomy and location suggest that our appendix could selectively harbor beneficial microbes and prevent their contamination from potential pathogens in the fecal stream. Further, our appendix is rich in lymphoid tissue (Gut-Associated Lymphoid Tissue; GALT) and thereby rich in IgA and mucin. Bollinger et al show that IgA and mucin in turn provide a rich milieu that supports mutualistic biofilms of beneficial microbes. Bollinger et al propose that our appendix is optimally located and structured for maintaining gut bacteria in a protected manner from peristalsis-propelled expulsion.

As Laurin et al propose in the figure above (The Cecal Appendix: One More Immune Component With a Function Disturbed By Post-Industrial Culture), when infected, the gut uses diarrhea to purge the infection. Unfortunately, this eliminates beneficial microbes as well. They propose that during such purges, location and anatomy protect appendix-associated microbiota that are then ideally positioned to re-inoculate back into the now microbe-depleted colon. This theory ingeniously accounts for anatomy, position and physiology in proposing this novel function. Each aspect of our appendix considered in such fashion lends plausibility to the theory.

Another striking aspect of this story? Journal of Theoretical Biology and The Anatomical Record, respectable scientific publications though they may be, are not the journals an immunologist would likely think of when asked to list top-tier immunology journals. That honor goes to journals like Nature, Science, Nature Immunology, Immunity, The Journal of Experimental Medicine and their ilk. Yet this remarkably plausible theory did not originate on their august pages. As Anton Ego indelibly points out in the Pixar animated film Ratatouille (film), "Not everyone can become a great artist; but a great artist can come from anywhere". This theory published in a relatively low profile journal was even considered plausible enough to attract the attention (Your Appendix Could Save Your Life | Guest Blog, Scientific American Blog Network) of a major popular scientific magazine, Scientific American.

Even with her giddy extravaganza, Nature is purpose-driven parsimony personified. Yet, we looked at our finger-like appendix and thought expendable. It's inflamed? Cut it out. Our appendix could be a poster child metaphor for our foolhardy predilection for overlooking the important in life. I learned anew to question received wisdom after reading William Parker et al's ingenious new theory for the function of our appendix. This particular story reveals an emblematic truth about scientific discovery and the shaky ground of the much-vaunted scientific objectivity. Science is built on successive paradigms and a given paradigm reflects the popular culture of its times. Our appendix conveniently became an expendable organ when our culture was dominated by the idea of expendability. Now it's a "safe house" for symbiotic gut bacteria. Genius lies in teasing out a truth that stands the test of time. I hope this is the case for William Parker et al's proposed new immune function for our appendix.

*: pun intended

http://tirumalaikamala.quora.com/Our-appendix-expendable-no-more-An-allegory-that-scientific-ideas-reflect-the-culture*-of-their-times




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