29 August 2012

Less than perfect: Harrison's Ch. 104 "Disorders of Hemoglobin"

Note: While I attempt to read the 397 chapters of Harrison's Principles of Internal Medicine, I am writing occasional reflections.

Paradoxically, some parts of our body work best when they fail under stress.
An illustrative story from my freshman year of college:

I decided to buy a wheelie chair for my (miniscule) dorm room from a student who lived 1.5 miles away. How could I transport the chair across campus when I didn't have a car?

I didn't feel like wasting an hour walking there and then walking the chair back. Instead, I elected to waste three hours dreaming up and building an alternative. I decided I would tow the chair with my bicycle by running a rope between them. The only rope I could find, though, was an Ethernet cable that was too short. I improvised, tying the cable to my bike rack and then lengthening the contraption by adding some plastic hangers as a kind of towing hitch. A friend grabbed a chair and took it for a test ride (below).

After a few modifications, the setup worked surprisingly well. So long as I didn't decelerate or turn suddenly, the chair trailed the bike by a comfortable four feet.

I bought the wheelie chair and sped it through the streets and paths of campus, dodging parked cars and drawing whistles and shouts of approval from onlookers. Two-thirds of the way through my journey, though, things went wrong. I steered my bike to the left of a bollard, and the chair instead traveled to the bollard's right. I watched helplessly as the line went taut and then snapped, pulverizing the hangers into a shower of plastic shards.

While cleaning up the mess, I realized with a shudder that my originally-intended design (a simple rope connecting chair to bike) could have seriously injured me. The plastic hangers had dissipated the tremendous shock by shattering and by disconnecting my bike from the chair. Had nothing been there to absorb the shock, my bike would have been flipped backwards, throwing me onto the cement headfirst and onto my back. Oddly enough, my design flaw saved me.
A similar phenomenon, of the "useful design flaw," underlies some of the disorders of hemoglobin. Hemoglobin is the critical enzyme in our red blood cells that carries oxygen to our tissues and carries carbon dioxide to our lungs. Hemoglobin disorders such as sickle-cell trait and thalassemia minor are particularly prevalent in areas endemic to malaria, and for good reason. Put simply, in these diseases hemoglobin is either mutated or unevenly manufactured, weakening the red blood cell. These weak blood cells are less hospitable to infection by the parasite (Plasmodium falciparum) that causes the most lethal form of malaria. And so, for those living in areas plagued by malaria, having weak blood cells is adaptive and life-prolonging.

Examples of other helpful design flaws abound in nature. Hepatitis C and HIV replicate their genomes with significantly lower fidelity than do humans. The numerous mutations generated by these replication errors help the viruses elude our immune systems and frustrate our attempts at making a vaccine.

My classmates and I are striving to become physicians who don't make mistakes. Nature, though, doesn't have to set so high of a bar for itself. Sometimes, less than perfect is just right.