Previous
Introduction
Themes
Key
LitCharts assigns a color and icon to each theme in Survival of the Sickest, which you can use to track the themes throughout the work.
Evolution and Illness
Interspecies Connectivity and Adaptation
Environment, Ancestry, and Race
Genetic Expression, Acquired Traits, and Mutation
Interdisciplinary Science and Research
Summary
Analysis
In 1997, Aran Gordon, a top financial executive and marathon runner, began to train for the Marathon des Sables, a brutal 150-mile race across the Sahara Desert. As he trained, he experienced physical difficulty running: his joints hurt and his heart skipped a beat. He went to multiple doctors, but they were unable to determine what might be wrong, or they gave him incorrect diagnoses. After three years, they finally discovered the real problem: there were massive amounts of iron in his Aran’s blood and liver. —he was “rusting to death.”
Much like Moalem shared his and his grandfather’s experiences in the introduction, here Moalem begins the main part of the book with a personal angle of the disease that he is about to discuss. He illustrates the fear and problems inherent in the doctors’ lack of knowledge, both in diagnosing the diseases and in figuring out how to treat Aran. In this way, Moalem shows how, when the root cause of an illness is unknown, it can derail a person’s life and stump even medical experts.
Themes
Hemochromatosis is a hereditary disease that disrupts the metabolization of iron in the body, causing it to build up in the blood, joints, and major organs. Unchecked, hemochromatosis can lead to liver failure, heart failure, and diabetes. It ultimately proves fatal if untreated. Hemochromatosis was thought to be incredibly rare until 1996, when the gene that caused the condition was isolated. Since then, scientists have discovered that the gene for hemochromatosis is the most common genetic variant in people of Western European descent.
Moalem sets up the idea that hemochromatosis is a very dangerous disease, but also that it is an incredibly common genetic mutation. Establishing the harm that it can cause will then allow Moalem to explore why it might have remained in the gene pool. He also provides a hint in letting readers know that the condition is common in people of Western European descent, as it suggests that it may have once provided this specific population with an advantage.
Themes
Moalem poses the question of why a deadly disease like hemochromatosis be part of so many people’s genetic codes. He reminds readers of how natural selection works: if a genetic trait makes an organism stronger, that organism is more likely to survive, reproduce, and pass that trait on. If a trait makes an organism weaker, that organism is less likely to survive, reproduce, and pass that trait on. Over time, species “select” traits that make them stronger. Moalem then answers his first question with another question, asking the reader whether they would agree to take a drug they knew would kill them in 40 years if it was the only thing that would prevent them from dying tomorrow.
Moalem lays out the foundation of evolutionary theory proposed by Charles Darwin: that traits which give an organism an advantage will be “selected for” because those organisms are more likely to survive, reproduce, and pass those traits on to keep them in the gene pool. This idea is integral to the book, and it will be repeated over each chapter as Moalem illustrates how some adaptations that appear negative have actually proved beneficial in the past, because they allowed people to survive and reproduce in the short term.
Themes
Moalem shifts to exploring humanity’s relationship with iron, which is an essential element for almost every function of our metabolism. Iron deficiencies are the most common cause of anemia, or low red blood cell count. Anemia can cause “fatigue, shortness of breath, and even heart failure.” Iron is also important to other forms of life: oceans that are rich in iron develop reefs and other ecosystems, while oceans without it are essentially lifeless.
The necessity of iron for life-forms living in vastly different environments suggests that all species on Earth are fundamentally connected in their evolutionary adaptations. Given Moalem’s previous question about short-term versus long-term survival, his observation that a person can have too little iron (anemia) as well as too much iron (hemochromatosis) suggests that there may be potential short-term advantages to having abnormal iron levels on either end of the spectrum—even if, in the long term, these conditions are dangerous.
Themes
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Because iron is so important, the food industry currently supplements almost everything with iron. But Moalem warns that this may be too much of a good thing: bacteria, cancer cells, and other parasites also need iron, and they can use the iron in our blood and tissue to survive. In 1952, a microbial researcher named Eugene D. Weinberg proved that iron helps nearly all bacteria multiply freely.
Moalem shows how parasites, bacteria, and viruses have adapted based on our biology. Because our blood and tissue are rich in iron, harmful pathogens use this as a means of invading and growing stronger using our own resources. In this way, Moalem demonstrates that species tend to evolve and adapt in tandem despite the vast differences among them.
Themes
Because iron can have potentially lethal effects, we also have iron-related defense mechanisms. Iron is not found in key areas where infection can enter our bodies: the eyes, mouth, nose, ears, and genitals. These openings also have fluids with proteins called chelators which bind to iron molecules, preventing them from being used. Additionally, when we are beset by illness, our bodies lock our iron away from biological invaders.
Because parasites, bacteria, and viruses have adapted to start using the iron in human tissues, we have, in turn, developed defense mechanisms to try and combat their ability to access to our iron. This again illustrates how dependent the evolutions of various species are on one another, spurring adaptation in a kind of feedback loop.
Themes
Moalem takes another detour to the 14th century, as the bubonic plague swept across Europe. More than 25 million people were killed: between one-third and one-half of the continent’s population. The bacterium that’s thought to have caused the plague, Yersinia pestis, caused painful swelling in the lymph nodes until they burst through the skin. New research indicates that the more iron in a given population, the more vulnerable that population was to the plague. Healthy adult males were most at risk because they were the group with the least amount of iron deficiencies. They were twice as likely to die as women of the same age because menstruation, pregnancy, and breast-feeding all led to iron deficiencies, and children and the elderly were also prone to malnourishment.
Here, Moalem begins to tie hemochromatosis and our reliance on iron to our history. Though on its surface, research done on the Bubonic plague may not appear to relate to genetics or evolution, it actually provides insight as to why certain people might have had an advantage over others in surviving the plague. It is also a direct example of Moalem’s previous point that humans have developed defense mechanisms and adaptations in response to bacteria’s ability to take advantage of our iron.
Themes
Moalem then returns to hemochromatosis. Even though people with hemochromatosis have far more iron in their systems, it isn’t distributed evenly in the body. While most cells end up with too much iron, white blood cells called macrophages have much less iron than others. Macrophages work like the law enforcement of the immune system, as they try to identify pathogens and destroy them.
Here Moalem isolates the key benefit of hemochromatosis: even though iron builds up in a harmful way, its depletion in one area of the body provides a benefit. This further illustrates his point that although diseases like hemochromatosis can cause serious health issues in the long term, they can inadvertently protect people from acute problems (like infectious disease) in the short term.
Themes
In a non-hemochromatic person, macrophages have plenty of iron, and infectious agents can use that iron to feed and multiply. But for those with hemochromatosis, whose macrophages do not have iron, the plague was unable to gain that strength, and therefore those people were able to combat the bacteria better and were more likely to survive. Even though hemochromatosis is ultimately harmful, being able to survive in the short term is more important because it allows people to reproduce.
Moalem combines the information he has presented on hemochromatosis and how bacteria and parasites interact with the iron in our blood, thus illustrating how hemochromatosis was actually selected for during the Black Plague because it gave those with the condition an advantage in being able to survive and reproduce.
Themes
Recent research suggests that hemochromatosis originated with the Vikings and may have actually evolved as a protective measure against iron deficiency. Some posit that Viking men may have offset the negative effects of hemochromatosis because their warrior culture resulted in frequent blood loss, which prevents the buildup of iron in the blood. As the Vikings colonized and settled on the European coastline, they passed on the condition to their offspring. Then, when the black plague began to sweep across Europe, those of Viking descent were much more likely to survive the plague, reproduce, and pass the mutation on to their children, which also gave them more resistance to subsequent outbreaks.
Moalem also examines the benefits of hemochromatosis in Vikings, illustrating how it could have held advantages even before the Black Plague because it guarded against anemia. Additionally, the negative aspects of hemochromatosis were even further offset by the unintentional bloodletting that naturally arose in the culture. Because they were then able to pass the trait on, and the trait was amplified by the Black Plague, Moalem illustrates how genetic conditions can be compounded by a variety of social and biological conditions.
Themes
This new understanding of hemochromatosis has prompted a change in perspective regarding two long-used medical treatments: bloodletting and iron dosing. Bloodletting is one of the oldest medical practices, derived from the thinking of the Greek physician Galen. He theorized that all illness resulted from an imbalance of the four “humors”: blood, black bile, yellow bile, and phlegm. Thus, if someone had an illness, doctors balanced the fluids through fasting, purging, and bloodletting. Yet the excessive use of bloodletting in the 18th and 19th century was ultimately proven to be largely harmful. By the 20th century, most viewed the practice as a brutal example of prescientific medicine, and it was largely discontinued.
Moving on from bloodletting was considered to be a progressive development in medicinal practice, informed by new scientific discoveries. It was largely caused by the germ theory taking precedence over the theory of the four humors in understanding illness. This led to an important and novel understanding of how bloodletting was not helpful in every incidence of illness, as had been previously practiced.
Themes
Yet Moalem argues that the way bloodletting was broadly discredited may have been misguided. Bloodletting is actually the treatment of choice for hemochromatosis, as bleeding prevents iron buildup in the body’s organs. It can also be used to combat heart disease, high blood pressure, and pulmonary edema. In moderation, bloodletting may have a beneficial effect because it reduces the amount of iron available for pathogens to feed on.
New understanding of hemochromatosis and the way that it can be helpful in combatting the Black Plague opened the door to understanding that bloodletting might be the proper treatment. In turn, this advancement in evolutionary understanding also led to the recognition that bloodletting might achieve the same beneficiary effect for other ailments. This allowed the medical community to reevaluate the dismissal of bloodletting and recognize that (just the like the diseases it was used to treat) it may, in fact, have some advantages.
Themes
Conversely, findings have called into question the practice of treating those with anemia with iron loading. A doctor named John Murray was working in a Somali refugee camp when he noticed that most of the Somali people had pervasive anemia—and despite the fact that they were exposed to a range of virulent pathogens, they were relatively uninfected. But when Murray started to treat some of the population with iron, their rate of infection skyrocketed. In another example, 35 years ago, doctors in New Zealand routinely injected Maori babies with iron supplements to prevent anemia. These children were then seven times more likely to suffer from potentially deadly infections as those who did not receive the injections.
Additionally, understanding how a lack of iron can actually be beneficial, in the way that Moalem is laying out here, can help people avoid mistakes like the one that John Murray and the doctors in New Zealand made. A lack of iron actually provides a similar benefit to hemochromatosis, because it prevents disease from gaining access to the body’s iron. Together, these examples show that the more we understand about our own biological adaptations and how even seemingly disadvantageous traits can actually be helpful, the more successful we may be at keeping ourselves and others healthy.
Themes
Hemochromatosis and anemia aren’t the only hereditary diseases that have helped combat other conditions. The second-most common genetic disease in Europe is cystic fibrosis, which causes people to die young, often from lung-related illnesses. But new research suggests that carrying a copy of the gene that causes the disease offers some protection from tuberculosis—which caused 20 percent of all deaths in Europe between 1600 and 1900.
Moalem brings up yet another disease in the chapter that can have benefits despite its long-term harm: cystic fibrosis. This is another example of one disease being beneficial against another more deadly disease, proving how even though tuberculosis isn’t as much of a problem in today’s society, our mechanism for combating it has been bred into our genes.
Themes
It took Aran Gordon three years to learn that he had hemochromatosis. He was told that untreated, he would have five years to live. Today, Moalem writes, we know that the genetic disorder may have helped his ancestors survive the plague. Today, Aran’s health has been restored through bloodletting. Today, we understand much more about the relationship between our bodies, iron, and infection. Aran Gordon finished the Marathon des Sables for the second time in April 2006, a few months after he was supposed to have died.
Here, Moalem drives home his point by returning to the personal anecdote of Aran Gordon. Thanks to understanding about how hemochromatosis helped people survive the plague, the iron locking involved, and the renewed understanding of bloodletting, what once might have been a debilitating or fatal disease is now something that Gordon can live with. The ability to synthesize this research now allows people to live healthier, longer lives—and that, Moalem implies, is the ultimate goal.
Themes
