Survival of the Sickest: The Surprising Connections Between Disease and Longevity. Jonathan Prince

symptoms, or they drew the wrong conclusion. When his illness left him depressed, they told him it was stress and recommended he talk to a therapist. When blood tests revealed a liver problem, they told him he was drinking too much. Finally, after three years, his doctors uncovered the real problem. New tests revealed massive amounts of iron in his blood and liver – off-the-charts amounts of iron.

      Aran Gordon was rusting to death.

      Hemochromatosis is a hereditary disease that disrupts the way the body metabolizes iron. Normally, when your body detects that it has sufficient iron in the blood, it reduces the amount of iron absorbed by your intestines from the food you eat. So even if you stuffed yourself with iron supplements you wouldn’t load up with excess iron. Once your body is satisfied with the amount of iron it has, the excess will pass through you instead of being absorbed. But in a person who has hemochromatosis, the body always thinks that it doesn’t have enough iron and continues to absorb iron unabated. This iron loading has deadly consequences over time. The excess iron is deposited throughout the body, ultimately damaging the joints, the major organs, and overall body chemistry. Unchecked, hemochromatosis can lead to liver failure, heart failure, diabetes, arthritis, infertility, psychiatric disorders, and even cancer. Unchecked, hemochromatosis will lead to death.

      For more than 125 years after Armand Trousseau first described it in 1865, hemochromatosis was thought to be extremely rare. Then, in 1996, the primary gene that causes the condition was isolated for the first time. Since then, we’ve discovered that the gene for hemochromatosis is the most common genetic variant in people of Western European descent. If your ancestors are Western European, the odds are about one in three, or one in four, that you carry at least one copy of the hemochromatosis gene. Yet only one in two hundred people of Western European ancestry actually have hemochromatosis disease with all of its assorted symptoms. In genetics parlance, the degree that a given gene manifests itself in an individual is called penetrance. If a single gene means everyone who carries it will have dimples, that gene has very high or complete penetrance. On the other hand, a gene that requires a host of other circumstances to really manifest, like the gene for hemochromatosis, is considered to have low penetrance.

      Aran Gordon had hemochromatosis. His body had been accumulating iron for more than thirty years. If it were untreated, doctors told him, it would kill him in another five. Fortunately for Aran, one of the oldest medical therapies known to man would soon enter his life and help him manage his iron-loading problem. But to get there, we have to go back.

      Why would a disease so deadly be bred into our genetic code? You see, hemochromatosis isn’t an infectious disease like malaria, related to bad habits like lung cancer caused by smoking, or a viral invader like smallpox. Hemochromatosis is inherited – and the gene for it is very common in certain populations. In evolutionary terms, that means we asked for it.

      Remember how natural selection works. If a given genetic trait makes you stronger – especially if it makes you stronger before you have children – then you’re more likely to survive, reproduce, and pass that trait on. If a given trait makes you weaker, you’re less likely to survive, reproduce, and pass that trait on. Over time, species “select” those traits that make them stronger and eliminate those traits that make them weaker.

      So why is a natural-born killer like hemochromatosis swimming in our gene pool? To answer that, we have to examine the relationship between life – not just human life, but pretty much all life – and iron. But before we do, think about this – why would you take a drug that is guaranteed to kill you in forty years? One reason, right? It’s the only thing that will stop you from dying tomorrow.

      Just about every form of life has a thing for iron. Humans need iron for nearly every function of our metabolism. Iron carries oxygen from our lungs through the bloodstream and releases it in the body where it’s needed. Iron is built into the enzymes that do most of the chemical heavy lifting in our bodies, where it helps us to detoxify poisons and to convert sugars into energy. Iron-poor diets and other iron deficiencies are the most common cause of anemia, a lack of red blood cells that can cause fatigue, shortness of breath, and even heart failure. (As many as 20 percent of menstruating women may have iron-related anemia because their monthly blood loss produces an iron deficiency. That may be the case in as much as half of all pregnant women as well – they’re not menstruating, but the passenger they’ re carrying is hungry for iron too!) Without enough iron our immune system functions poorly, the skin gets pale, and people can feel confused, dizzy, cold, and extremely fatigued.

      Iron even explains why some areas of the world’s ocean are crystal clear blue and almost devoid of life, while others are bright green and teeming with it. It turns out that oceans can be seeded with iron when dust from land is blown across them. Oceans, like parts of the Pacific, that aren’t in the path of these iron-bearing winds develop smaller communities of phytoplankton, the single-celled creatures at the bottom of the ocean’s food chain. No phytoplankton, no zooplankton. No zooplankton, no anchovies. No anchovies, no tuna. But an ocean area like the North Atlantic, straight in the path of iron-rich dust from the Sahara Desert, is a green-hued aquatic metropolis. (This has even given rise to an idea to fight global warming that its originator calls the Geritol Solution. The notion is basically this – dumping billions of tons of iron solution into the ocean will stimulate massive plant growth that will suck enough carbon dioxide out of the atmosphere to counter the effects of all the CO₂ humans are releasing into the atmosphere by burning fossil fuels. A test of the theory in 1995 transformed a patch of ocean near the Galápagos Islands from sparkling blue to murky green overnight, as the iron triggered the growth of massive amounts of phytoplankton.)

      Because iron is so important, most medical research has focused on populations who don’t get enough iron. Some doctors and nutritionists have operated under the assumption that more iron can only be better. The food industry currently supplements everything from flour to breakfast cereal to baby formula with iron.

      You know what they say about too much of a good thing?

      Our relationship with iron is much more complex than it’s been considered traditionally. It’s essential – but it also provides a proverbial leg up to just about every biological threat to our lives. With very few exceptions in the form of a few bacteria that use other metals in its place, almost all life on earth needs iron to survive. Parasites hunt us for our iron; cancer cells thrive on our iron. Finding, controlling, and using iron is the game of life. For bacteria, fungi, and protozoa, human blood and tissue are an iron gold mine. Add too much iron to the human system and you may just be loading up the buffet table.

      In 1952, Eugene D. Weinberg was a gifted microbial researcher with a healthy curiosity and a sick wife. Diagnosed with a mild infection, his wife was prescribed tetracycline, an antibiotic. Professor Weinberg wondered whether anything in her diet could interfere with the effectiveness of the antibiotic. We’ve only scratched the surface of our understanding of bacterial interactions today; in 1952, medical science had only scratched the surface of the scratch. Weinberg knew how little we knew, and he knew how unpredictable bacteria could be, so he wanted to test how the antibiotic would react to the presence or absence of specific chemicals that his wife was adding to her system by eating.

      In his lab, at Indiana University, he directed his assistant to load up dozens of petri dishes with three compounds: tetracycline, bacteria, and a third organic or elemental nutrient, which varied from dish to dish. A few days later, one dish was so loaded with bacteria that Professor Weinberg’s assistant assumed she had forgotten to add the antibiotic to that dish. She repeated the test for that nutrient and got the same result – massive bacteria growth. The nutrient in this sample was providing so much booster fuel to the bacteria that it effectively neutralized the antibiotic. You guessed it – it was iron.

      Weinberg went on to prove that access to iron helps nearly all bacteria multiply almost unimpeded. From that point on, he dedicated his life’s work to understanding the negative effect that the ingestion of excess iron can have on humans and the relationship other life-forms have to it.

      Human iron regulation is a complex system that involves virtually every part of the body. A healthy adult usually has between three and four grams of iron in his or her body. Most of this iron is in the bloodstream within hemoglobin, distributing oxygen,