Survival of the Sickest

There was a Daily Show episode last month, where Jon Stewart interviewed Dr. Sharon Moalem about his new book, "Survival of the Sickest." The topic of his book -- that many human diseases persist because they actually confer a survival advantage -- is a recurring theme in medical school, and always something fun to ponder. Stewart asked some straightforward questions, Moalem gave answers designed to flabbergast the lay audience (along the lines of,"Our bodies can rust with iron overload! But we should be thankful we sequester iron so fastidiously, because otherwise bacteria would feast on it, like they did during the Plague!")

Unfortunately, Moalem didn't have much time to flesh out his ideas, because Stewart, mindful of the audience, kept jumping around.

I noticed that Moalem wore a yarmulke during the interview, and wondered if he worked at my hospital. Indeed, he does. The very next day, a publishing agent contacted me, offering to send a copy of Moalem's book if I'd review it online . I agreed, and made a mental note to finish the last two books that were sent to me under similar arrangements (yes, blogging's been good to me, Howard).

But Survival of the Sickest had something going for it that those other books did not -- a long bus trip in which I could sit and read the thing. And it's a quick read, chock full of tidbits and groan-inducing puns.

Others have pointed out similarities to last year's cocktail-party companion, Freakonomics. Levitt and Dubner's book was about how clever approaches to problems can yield surprising answers. There was no overarching hypothesis. Sickest is a little more organized -- but not much more.

Moalem uses a few big examples to support the idea that some long-term diseases can provide short-term benefit -- hemochromatosis as a way or warding off bacterial infection, diabetes as a defense against frostbite, and thalassemia, sickled cells, and G6PD deficiency as protection from malaria. All these subjects are treated airily, with a smattering of supporting evidence, and no real consideration of criticism.

That's ok. This book isn't really about proving a hypothesis. In fact, it truly shines in its asides and extraneous information. One chapter, "The Cholesterol Also Rises," tries to build the case that Africans experience high cholesterol (and its associated risks) because that's nature's compensation for developing darker skin. Darker skin means it's harder for the body to make Vitamin D, but extra cholesterol building blocks would help the process along.

What makes the chapter really memorable, though, are little tidbits about race, skin color, how light can trigger sneezes, and the explanation for the Asian flush when drinking alcohol. One aside featured the pituitary gland, which ultimately triggers the melanocytes that tan the skin. The pituitary responds to the optic nerve's sensation of light -- so tanning with sunglasses is actually less effective than keeping your eyes wide open to the sun.

I love that stuff, and dog-ear pages with factoids that I'll want to recall. Sickest had over two dozen dog-ears by the end, which is right up there with Freakonomics and Gladwell's books.

It was enough to make me overlook the really tenous evidence Moalem uses to support his most contentious theory -- that diabetes' prevelance is an adaptation to the last ice age. Sure, it's more common in among Northern Europeans. And sure, some frogs use hyperglycemia as an antifreeze during hibernation season.

But he also invokes the fact that rats become insulin-resistant in the cold, and that human fibrinogen levels rise in winter (which he also links to our higher rate of MI and stroke). These may not be so much cold responses as a simple molecular kinetics -- a lot of biochemical reactions don't work as well in cold temeperatures. Besides, he says high fibrinogen in winter is evolution's way of protectiong against ice-crystal damage, but he fails to note that clotting is impaired by hypothermia -- clotting factor levels are not correleted with activity.

Moalem cites the fact that type I diabetes is most often diagnosed in the autumn, when "temperatures start to fall." Well, I've heard this tidbit before, but it was used to support the viral theory of type I diabetes -- and frankly, that theory has a lot more support. Moalem doesn't mention it.

The book's final chapters don't even try to support his idea that chronic disease may help in the short term. The chapters just funnel Moalem's extensive knowledge of evolutionary biology trivia to the reader. And it's entertaining. I'd heard some stuff on the blogosphere about toxoplasmosis influencing rat behavior, and potentially human behavior, too -- but Moalem is able to expand upon it and put it in context. Also, he includes a nice section on the Aquatic Ape hypothesis, which I plan to share with my friend's wife before she gives birth in a spa this summer.

So, this book certainly gave me some things to think about and file away. But in an anecdote that's fairly typical, Moalem notes that in times of societal stress (such as former East Germany in 1990 and the US in the fall of 2001) women are more likely to miscarry -- but only the male fetuses. Interesting, isn't it? Is it because males are more demanding on resources? Or because in a crisis, it's better to have more females around to ensure survival?

It turns out no one knows. It's not even clear how it's happening. Evolutionary biology can give us some possible explanations, all of which can be satisfying from a teleologic perspective. But unfortunately, none of them may be the right answer. None of them may advance our understanding or treatment of disease. Still, it makes for great conversation.

Sitting in a Tin Can

Pushing tPA feels a lot like coordinating a space shuttle launch. There's such a long checklist to work through before this powerful clotbuster can be administered -- and the drug is so dangerous that if any contraindication is found, the show's off.

The other day, our little corner of the ER sounded like mission control:

The patient's family reported that stroke onset was within our three hour window.

The medical record revealed no recent surgeries or history of intracranial bleed.

The nurse noted the systolic blood pressure had fallen below 185 mmHg.

The radiologist phoned in the negative head CT results.

The neurologist confirmed our patient's weakness and lopsided smile weren't improving.

The emergency medicine resident emerged from behind the curtain to proclaim, "guaiac negative!"

And we were go for tPA.

The only difference is, compared to the fire and noise of a NASA launch, the stopcock and syringe of tPA is a little anticlimactic. Ten percent of the drug goes in as a bolus, then the remaining 90% as a drip over an hour.

During that hour, the neuro resident made arrangements for our patient, upstairs in the stroke unit. I went back to seeing other patients.

When the tPA drip ended, as the nurses set up the portable monitor, I checked in again on our patient. Her pupils were still equal and reactive , but her left side was still weak. As far as I could tell, the medication hadn't done any harm, but didn't seem to have done any good, either.

I wheeled her out of the department, into the elevator, and we glided up to the unit. Her family members rode along, silently.

The elevator doors opened, and the neuro resident greeted us. I handed over her chart and said goodbye to the patient. Her family thanked me, and she acknowledged me -- with a bright, symmetric smile.