Q & A: An Evolutionary Curiosity

Gut check: Parker, shown holding a

Gut check: Parker, shown holding a "tissue culture cassette" used in his study of digestive-tract bacteria, provides a glimpse into the importance of the appendix. Megan Morr

Scientists have long pondered the evolutionary purpose of the appendix, a tiny organ attached to the intestine that sometimes becomes inflamed and has to be surgically removed. Bill Parker, assistant professor of experimental surgery at Duke, believes he and his colleagues have stumbled upon the answer. As a biochemist and immunologist, Parker studies immune-system functions on a microscopic level. Since the mid-1990s, his research has focused on the way that the immune system interacts with the "good" bacteria that live in the gut. According to his theory, the appendix plays a key role in sheltering those bacteria in times of crisis, thereby helping the system to re-boot. He took a break from dissecting a rabbit appendix in the lab to answer some questions.

So how does the appendix work?

The idea is that the appendix is a safe house or a storehouse, even a cultivation center for the normal, beneficial bacteria that our gut needs. That safe house would be necessary and useful in the event that the main compartment of bacteria, the large bowel, got contaminated with some kind of infectious organism and got flushed out. From all the signals we're getting from the scientific community, it looks like we may be right on target.

How did you first get interested in solving the mystery of the appendix?

We never cared about the appendix. We were, and still are, more interested in inflammatory bowel disease and how the immune system interacts with the bacteria in the gut. We started working on that back in 1996. In the course of that, we, along with Jeff Gordon's laboratory, really figured out that the immune system supports bacterial growth in the gut. [Gordon is a professor and directs the Center for Genome Sciences at Washington University in St. Louis.] That was a real paradigm shift in the field, really novel thinking. We published papers in 2003 and 2004 looking in detail at the issue, and it just so happened that the best human tissue we could get was the human appendix.

What do you mean by that, the best human tissue?

To examine the bacteria in the gut, you really need very fresh tissue. It turns out that people periodically have their appendix removed even when it's a normal appendix. And we could get access to those appendices, which we did. That was really the only way that we could get fresh tissue to study that was free of disease.

What did you see when you got that tissue?

What we see are "biofilms," in other words, adherent colonies of bacteria that are growing on the inner lining of the appendix. We eventually did get fresh tissue from the rest of the digestive tract, and you don't find those kinds of biofilms. You find some, but they're not as good, not as thick, not as consistent, as they are in the appendix.

The appendix is about the size of your pinky, five or ten centimeters in length, and it has a narrow opening, almost like a little pencil lead. In fact that's probably important for the function. It was already known that it has a lot of immune tissue associated with it. When you put that information together—that the immune system supports the growth of bacteria in the gut and that biofilms, the mode of growth that's supported by the immune system, are most prevalent in the appendix—with everything we already knew about the appendix, you come to this, in retrospect, obvious conclusion that the appendix is there as a storehouse for bacteria.

So what happens when the system, as you say, gets flushed?

Periodically, bacteria get shed out of the appendix. Those bacteria, in microbiology terms, would re-inoculate the system. They would reboot the system and help those good bacteria get growing again.

If the appendix does seem to serve this important purpose, then why is it that we can have our appendix taken out and be perfectly healthy?

We have the Centers for Disease Control in this country, and we have sewer systems. We have running hot water, we have antiseptics everywhere. We have all of these amazing things which keep us clean. Diseases that cause epidemics of dysentery are not that common, and when somebody does get a disease, food poisoning, or something like that, they get medical treatment. The population as a whole is not in danger of losing its good bacteria.

But in Third World countries, there are three major diseases that are killers of human beings. One is HIV, which is very recent. Then pneumonia, and then things that cause diarrhea. There are no sewer systems, so when an infectious organism gets into the water supply near a village, everybody's going to catch the disease, whatever the disease is.

It sounds like people in Third World countries face a major dilemma in terms of how to deal with cases of appendicitis, if their appendices still serve an important role.

There are no surgeons to speak of, so you don't have access to surgery. But I might add that appendicitis is one of those diseases that is associated with a hygienic environment.

Sometimes something gets stuck in there and it gets inflamed. But sometimes, even with nothing stuck in there, it can just get inflamed. There's something called the hygiene hypothesis that's been around for decades. The idea is, if your immune system isn't stimulated by something dangerous in your environment, it is going to react against something else, whether it's a pollen grain that causes allergies, or your own tissue leading to autoimmune disease, or maybe it's something in the gut leading to appendicitis.

There have been a lot of stories in the news recently about the rise in food allergies among children, where their bodies are fighting off, say, peanuts.

Appendicitis is the same thing. David Barker, a British epidemiologist, is the guy who really nailed down the issue, at least in Britain. He found out when you get running hot water in your house, as a community, then you have an epidemic of appendicitis.

Every time I talk with somebody about this, I think it's really important to say that even though the appendix has a function, if you have that pain in the lower-right quadrant, get it taken out. Because it's life-threatening if you don't get it taken out, and you really don't need it in this culture.

Do you still have your appendix?

Yes, I still have mine.

Then it's easy for you to say.

Yeah, easy for me to say. I think my dad is missing his.

Earlier, you were dissecting a rabbit's appendix. Do all animals have them?

Other animals that have an appendix are the Great Apes, other primates closely related to humans, the opossum, the wombat. There's a rodent that lives in Africa, called the mole-rat, that has an appendix. And rabbits.

Do those work in a similar way?

Yes. We've even looked in animals that don't have an appendix at all, and there's a part of the gut in those animals called a cecum. It serves as a digestive organ, but if you look at how the biofilms are laid out in those animals, as you get further and further into the back end of the gut, you find a lot more biofilms. We've looked at mice, rats, humans, and done a little bit of work in nonhuman primates. It looks like, across the board [in mammals], there's something there, probably not as effective as the appendix, that maintains and harbors those beneficial bacteria.

We're really interested in looking at how common this is. We're working with some evolutionary biologists, looking at this layout across the animal kingdom. We're looking at frogs later today on a microscope.

This whole thing came about because we were working with [professor] Randy Bollinger [Ph.D. '77, M.B.A. '97], who's a surgeon. I'm looking at the molecules, and how this particular molecule interacts with this receptor on a bacterium, and beginning to understand how the immune system supports bacterial growth, how the further back you go, the better the bacteria get supported in their biofilms. Meanwhile, one of his jobs is to take out appendices, and he was just thinking about it in a group meeting: What could the appendix be for? And a light bulb came on, and he said, "You know, I bet I know what the appendix is for." And before he even said what he was thinking, I knew.

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