Is the appendix a vestigial organ?

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How evolution is applied to diseases changes over time. At least three ideas have been pitched to explain why we have an appendix, from an evolutionary perspective.

1) The appendix is a vestigial organ, no longer useful, that is derived from a larger structure in a common ancestor shared by humans and other apes. Charles Darwin is among those who proposed this possibility.

Darwin suggested that the distant ancestors of humans and other apes survived on a herbivorous diet rich in leaves, and thus needed a large cecum, the part of the gut that houses bacteria specialized in the breakdown of plant fiber. Darwin speculated that an enlarged cecum was no longer necessary when human ancestors shifted to a more easily-digested diet, mostly fruit.  Darwin thought the appendix shrank when it had no longer had a useful function. This viewpoint was  on display in a delightful book that I just discovered, entitled “Evolution and Disease,” by Sir John Bland-Sutton, published in 1895. (This book takes a cross-species comparative approach to disease that has also inspired more recent works such as Zootopia by Barbara Natterson-Horowitz). In Bland-Sutton‘s chapter “Vestigial Parts” the appendix is described as: “a typical example of a functionless part, and, like an idle person in a community, is not infrequently a source of considerable danger and suffering, and is responsible for a number of deaths annually.” (from appendicitis).

Evolution and Disease

2) The second view, not incompatible with the first, was expressed in G.C. Williams and Randolph Nesse in the 1994 book “Why We Get Sick.” They argue that selection would favor a smaller thinner appendix over time as it lost its function as a digestive organ. However, deaths from appendicitis would halt the further narrowing of the organ, favoring a larger appendix: “A bit of inflammation and swelling is less likely to disrupt the blood supply of a large appendix than that of a long thin one. Natural selection gradually reduces the size of the useless appendix, but any appendix narrower than a certain diameter becomes more vulnerable to appendicitis. Thus deaths from appendicitis may paradoxically select for a slightly larger appendix, maintaining this less than useless trait.”

Williams and Nesse note the logical flaw in this argument in the next sentence:

” Selection is also almost certainly very slowly making the appendix shorter, but in the meantime the appendix may be maintained by the shortsightedness of natural selection.”

3) A third option is that natural selection is not shortsighted, but instead that a positive selection favors the presence of an appendix, increasing the survival of its bearers. This possibility has been argued by those who say that the appendix has a safehouse function for beneficial gut microbes.

In this view, the appendix provides a reservoir of beneficial microbes that can recolonize the gut after infectious diarrhea. In keeping with the view of a beneficial appendix, it has been suggested that the appendix evolved over 30 times in mammals.

Recently, the role of the appendix in protecting against recurrent infection was tested. Im and colleagues tested whether recurrence of Clostridium difficile was more common in patients who had had an appendectomy for appendicitis versus those who still had their appendix. Appendectomy increased the risk of recurrent severe diarrhea.

Read more about the study here

 

 

Hypotension as an adaptation in sepsis

From David Anderson in JEMS patient care:

“Recent research in sepsis has also hinted at a phenomenon thus far not even considered—that hypotension is an adaptive response, honed over millions of years of evolution, which may mean that we are actually making patients worse when we thought we were helping them.”

Read on

Flipping the classroom, FOAM, and evolution in medicine

In the spirit of flipping the classroom, there will be some changes coming to the Evolution Medicine blog. I will soon be posting short podcasts and videos that will be designed for students of the evolutionary medicine course. These podcasts are also aimed at emergency physicians (like myself) and trainees in a variety of specialties.

Visitors to this site will also see a greater emphasis on the practical application of evolutionary medicine to patient care and clinical research. I am inspired to make these changes by a growing movement of free open access medical education, which goes by the acronym FOAM.

Several leaders in the FOAM movement recently held a meeting, the SMACC conference, in Sydney Australia, that included a session on adaptation in critical care.

SMACC Adaptation Now, unfortunately, I missed this conference and have not heard these talks, but I will post my thoughts about these topics (and already have) over the next few weeks.

This is an exciting development, reinforcing the idea that evolutionary concepts, especially adaptation, can inform medical practice and research. I agree with this emphasis and the discussion that these ideas generate. Check back soon for additional links to the websites that feature these speakers.

For now, here are a couple examples: check out Life in the Fast Lane by Dr. Chris Nickson, an intensivist based in Melbourne Australia. Also visit Rob Mac Sweeney’s Critical Care Reviews

 

 

Adaptation in Critical Care

Last year Critical Care interviewed experts in the field, and asked what they predicted would be big ideas for the future.

I have posted an abbreviated response from John Marini MD of the University of Minnesota, whose idea revolved around the idea of adaptation in critical care medicine (I removed references from this excerpt). I don’t agree with everything he writes, but it is interesting to hear that a leader in critical care has proposed that advances may rely on taking an evolutionary view to the abnormalities seen in sepsis. Here it is:

After rescue, we should adapt patients to their critical illness physiology (J Marini)

“Critical care evolved from anesthetic approaches and postoperative practice. In elective cases, the sudden trauma of surgery interrupts resting physiology and is addressed by an attempt to restore a normal baseline. In the critical care setting, however, the price of maintaining normality may be injury inflicted by the therapy itself (ventilator-induced lung injury, drug toxicity, consequences of sedation, and so forth). Equally plausible is that our enforcing of normal indicators and protracted use of excessive support may impede the patient’s potential to adapt to the abnormal physiology that characterizes chronic critical illness.

Health is characterized by gradual transitions between physiological states, by variation of cardiorespiratory indices, and by continual adaptation to biochemical, environmental, and mechanical stressors. Acute disease, on the contrary, is often characterized by abrupt transitions, failure to adapt to the stressor, and monotonously inflexible physiological patterns. Currently, our treatments rescue very effectively, but when sustained for too long they may frustrate the patient’s innate adaptability to stressful but potentially survivable illness. For example, early use of short-term muscle relaxants enables lung-protective strategies and may reduce mortality risk in acute respiratory distress syndrome, but when sustained for too long muscle relaxants can cause muscular atrophy and sustained weakness. Because evolution did not provide for appropriate responses to severe acute injuries, an argument can be made that we must moderate the initial assault and response, and then build our capability to respond to lingering challenges over time.

During health, tolerable stresses above the resting baseline that are applied and released build strength, promote tolerance, and remodel tissues. Endurance athletes are a good example of what can be achieved with intermittent exposure to challenging stress. Stress-induced adaptations include enhanced pulmonary oxygen exchange, increased blood volume and hemoglobin concentration, enriched blood flow to skeletal muscle, improved thermal regulation, increased mitochondrial size and density, and increased capillarization of muscular beds. The healthy individual is also extremely adaptable when the physiologic milieu is gradually changed. Important lessons regarding adaptation to abnormal physiology have been learned from protracted exposure to hypoxic inspired gas, both in mountain climbing and in the experimental laboratory.”

Read the entire piece here at Critical Care v. 17 suppl. 1.

Fever redux

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It is somewhat remarkable that in 2014 people are still arguing about the role of fever in illness.

To recap, Matthew Kluger back in the early 1970s showed that a behavioral fever was critical in keeping lizards alive after experimental infection with gram-negative bacteria. Kluger subsequently showed that fever improves bacterial killing by immune cells.

Edmund Legrand and I wrote in 2012 that fever and other components of the acute phase response, evolved because you can tolerate the costs of having a fever better than the parasite can. That difference in capacity to absorb costs usually leads to survival from infection, and the increase in survival conferred by fever led to its evolution and persistence in a wide variety of organisms, as shown here: Clin Infect Dis. 2000 Oct 31(Supplement 5) S185-9, Figure 1. Even some invertebrate organisms exhibit a behavioral fever, including honeybees!

So why are people still arguing about the use of tylenol in the emergency department, clinic, and hospital? In fact, during my last shift, the nurse asked/informed me about giving tylenol to our febrile patient in the ED. (It was busy and I did not object). However, animal studies suggest that antipyretic use (aspirin) increases mortality from Streptococcus pneumoniae infection and in humans no evidence exists to support the use of antipyretics for sick patients.

There is an ongoing study that I do hope will help clear up any uncertainty once and for all. This is the HEAT trial, a randomized controlled trial of antipyretic paracetamol (tylenol) in critically ill patients, and is currently underway.

So, evolutionary medics, how do you think that trial will work out?  I’ll give my prediction here. IV paracetamol will not reduce mortality in these patients. I will not be surprised if mortality is increased in the treatment group.

So if fever is adaptive during infection, what would you say about a study that experimentally reduced temperature below normal for a life-threatening infection? Would you predict that this would be good or bad?

With the evidence that fever improves survival from infection, and evidence that fever is part of an adapative suite of changes during the acute phase response that improve bacterial killing, it would be hard to imagine that hypothermia would be beneficial in bacterial meningitis. Yet, that proposition was recently tested.

A randomized but not blinded trial of critically ill patients with bacterial meningitis compared experimental hypothermia versus no intervention. Guess what happened?

Are we surprised that the induced hypothermia group had excess mortality, causing the study to be terminated early for futility? (Click on the link above for the details and the complete JAMA article). I am not alone in thinking that hypothermia for infection is wrongheaded and dangerous.

The JAMA results are important, and show the value in publishing negative results (read about publication bias here), from which we can learn as much as positive findings.

Like you , I hope, I will be very interested in the results of the HEAT trial when they are published. And maybe I will put up more of a fight next time I’m asked to prescribe antipyretics in the emergency department (more on that later).

Joe Alcock MD

 

In appreciation of jazz great Horace Silver

“Musical composition should bring happiness and joy to people and make them forget their troubles.” Horace Ward Martin Tavares Silver

The only thing this post has to do with with evolution is the marvelous fact that Homo sapiens has evolved a capacity to create and enjoy music, especially hard bop jazz! Read a review about evolution of music appreciation here.

Horace Silver died today at 85 years of age. Just writing that brings  chills to my skin, sensations that are infused with sadness and a profound appreciation for my personal favorite jazz artist of all time. Take a moment to read about his remarkable and joyful life and listen to “Song for my Father” or his other masterpieces.

NPR

New York Times

Blue Note Records