SURVIVAL
OF THE SICKEST

THE SURPRISING CONNECTIONS BETWEEN

DISEASE AND LONGEVITY

DR. SHARON MOALEM

with Jonathan Prince

DEDICATION

To my grandparents Tibi and Josephina Elizabeth Weiss, whose lives served to teach me the complexities of survival

CONTENTS

Cover

Title Page

Dedication

Introduction

Chapter One: Ironing It Out

Chapter Two: A Spoonful of Sugar Helps the Temperature Go Down

Chapter Three: The Cholesterol Also Rises

Chapter Four: Hey, Bud, Can You Do Me a Fava?

Chapter Five: Of Microbes and Men

Chapter Six: Jump into the Gene Pool

Chapter Seven: Methyl Madness: Road to the Final Phenotype

Chapter Eight: That’s Life: Why You and Your iPod Must Die

Index

Acknowledgments

About the Author

Notes

Copyright

About the Publisher

INTRODUCTION

This is a book about mysteries and miracles. About medicine and myth. About cold iron, red blood, and neverending ice. It’s a book about survival and creation. It’s a book that wonders why, and a book that asks why not. It’s a book in love with order and a book that craves a little chaos.

Most of all, it’s a book about life – yours, ours, and that of every little living thing under the sun. About how we all got here, where we’re all going, and what we can do about it.

Welcome to our magical medical mystery tour.

When I was fifteen years old, my grandfather was diagnosed with Alzheimer’s disease. He was seventy-one. Alzheimer’s – as too many people know – is a terrible disease to watch. And when you’re fifteen, watching a strong, loving man drift away almost before your eyes, it’s hard to accept. You want answers. You want to know why.

Now, there was one thing about my grandfather that always struck me as kind of strange – he loved to give blood. And I mean he loved it. He loved the way it made him feel; he loved the way it energized him. Most people donate blood purely because it makes them feel good emotionally to do something altruistic – not my grandfather; it made him feel good both emotionally and physically. He said no matter where his body hurt, all he needed was a good bleeding to make the aches and pains go away. I couldn’t understand how giving away a pint of the stuff our lives depend on could make someone feel so good. I asked my high school biology teachers. I asked the family doctor. Nobody could explain it. So I felt it was up to me to figure it out.

I convinced my father to take me to a medical library, where I spent countless hours searching for an answer. I don’t know how I possibly found it among the thousands and thousands of books in the library, but something steered me there. In a hunch, I decided to plow through all the books about iron – I knew enough to know that iron was one of the big things my grandfather was giving up every time he donated blood. And then – bam! There it was – a relatively unheard of hereditary condition called hemochromatosis. Basically, hemochromatosis is a disorder that causes iron to build up in the body. Eventually, the iron can build up to dangerous levels, where it damages organs like the pancreas and the liver; that’s why it’s also called “iron overload.” Sometimes, some of that excess iron is deposited in the skin, giving you a George Hamilton perma-tan all year long. And as we’ll explore, giving blood is the best way to reduce the iron levels in your body – all my grand-father’s blood donations were actually treating his hemochromatosis!

Well, when my grandfather was diagnosed with Alzheimer’s, I had a gut instinct that the two diseases had to be connected. After all, if hemochromatosis caused dangerous iron buildups that damaged other organs, why couldn’t it contribute to damage in the brain? Of course, nobody took me very seriously – I was fifteen.

When I went to college a few years later, there was no question that I was going to study biology. And there was no question that I was going to keep on searching for the link between Alzheimer’s and hemochromatosis. Soon after I graduated, I learned that the gene for hemochromatosis had been pinpointed; I knew that this was the right time to pursue my hunch seriously. I delayed medical school to enter a Ph.D. program focused on neurogenetics. After just two years of collaborative work with researchers and physicians from many different laboratories we had our answer. It was a complex genetic association, but sure enough there was indeed a link between hemochromatosis and certain types of Alzheimer’s disease.

It was a bittersweet victory, though. I had proved my high school hunch (and even earned a Ph.D. for it), but it did nothing for my grandfather. He had died twelve years earlier, at seventy-six, after five long years battling Alzheimer’s. Of course, I also knew that this discovery could help many others – and that’s why I wanted to be a physician and a scientist in the first place.

And actually, as we’ll discuss more in the next chapter, unlike many scientific discoveries, this one came with the potential for an immediate payoff. Hemochromatosis is one of the most common genetic disorders in people descended from Western Europeans: more than 30 percent carry these genes. And if you know you have hemochromatosis, there are some very straightforward steps you can take to reduce the iron levels in your blood and prevent the iron buildups that can damage your organs, including the one my grandfather discovered on his own – bleeding. And as for knowing whether or not you have hemochromatosis – well, there are a couple of very simple blood tests used to make the diagnosis. That’s about it. And if the results come back positive, then you start to give blood regularly and modify your diet. But you can live with it.

I do.

I was around eighteen when I first started feeling “achy.” And then it dawned on me – maybe I have iron overload like my grandfather. And sure enough, the tests came back positive. As you can imagine, that got me thinking – what did this mean for me? Why did I get it? And the biggest question of all – why would so many people inherit a gene for something potentially so harmful? Why would evolution – which is supposed to weed out harmful traits and promote helpful ones – allow this gene to persist?

That’s what this book is about.

The more I plunged into research, the more questions I wanted answered. This book is the product of all the questions I asked, the research they led to, and some of the connections uncovered along the way. I hope it gives you a window into the beautiful, varied, and interconnected nature of life on this wonderful world we inhabit.

Instead of just asking what’s wrong and what can be done about it, I want people to look behind the evolutionary curtain, to ask why this condition or that particular infection occurs in the first place. I think the answers will surprise you, enlighten you, and – in the long run – give all of us a chance to live longer, healthier lives.

We’re going to start by looking at some hereditary disorders. Hereditary disorders are very interesting to people like me who study both evolution and medicine – because common conditions that are only caused by inheritance should die out along the evolutionary line under most circumstances.

Evolution likes genetic traits that help us survive and reproduce – it doesn’t like traits that weaken us or threaten our health (especially when they threaten it before we can reproduce). That preference for genes that give us a survival or reproductive advantage is called natural selection. Here are the basics: If a gene produces a trait that makes an organism less likely to survive and reproduce, that gene (and thus, that trait) won’t get passed on, at least not for very long, because the individuals who carry it are less likely to survive. On the other hand, when a gene produces a trait that makes an organism better suited for the environment and more likely to reproduce, that gene (and again, that trait) is more likely to get passed on to its offspring. The more advantageous a trait is, the faster the gene that produces it will spread through the gene pool.

So hereditary disorders don’t make much evolutionary sense at first glance. Why would genes that make people sick still be in the gene pool after millions of years? You’ll soon find out.

From there, we’re going to examine how the environment of our ancestors helped to shape our genes.

We’re also going to look at plants and animals and see what we can learn from their evolution – and what effect their evolution has had on ours. We’re going to do the same thing with all the other living things that inhabit our world – bugs, bacteria, fungi protozoa, even the quasi-living, that vast collection of parasitic viruses and genes we call transposons and retrotransposons.

By the time we’re through, you’ll have a new appreciation for the amazing collection of life on this amazing planet of ours. And – I hope – a new sense that the more we know about where we came from, whom we live with, and where they came from, the more we can do to control where we want to go.

Before you dive in, you need to discard a few preconceptions that you may have picked up before you picked up this book.

First of all, you are not alone. Right now, whether you’re lying in bed or sitting on the beach, you’re in the company of thousands of living organisms – bacteria, insects, fungi, and who knows what else. Some of them are inside you – your digestive system is filled with millions of bacteria that provide crucial assistance in digesting food. Constant company is pretty much the status quo for every form of life outside a laboratory. And a lot of that life is interacting as organisms affect one another – sometimes helpfully, sometimes harmfully, sometimes both.

Which leads to the second point – evolution doesn’t occur on its own. The world is filled with a stunning collection of life. And every single living thing – from the simplest (like the schoolbook favorite, the amoeba) to arguably the most complex (that would be us) – is hardwired with the same two command lines: survive and reproduce. Evolution occurs as organisms try to improve the odds for survival and reproduction. And because, sometimes, one organism’s survival is another organism’s death sentence, evolution in any one species can create pressure for evolution in hundreds or thousands of other species. And that, when it happens, will create evolutionary pressure in hundreds or thousands of other species.

That’s not even the whole story. Organisms’ interaction with one another isn’t the only influence on their evolution; their interaction with the planet is just as important. A plant that thrives in a tropical swamp has got to change or die when the glaciers slide into town. So, to the list of things that influence evolution, add all the changes in earth’s environment, some massive, some minor, that have occurred over the 3.5 billion years (give or take a few hundred million) since life first appeared on the planet we call home.

So to be crystal clear: everything out there is influencing the evolution of everything else. The bacteria and viruses and parasites that cause disease in us have affected our evolution as we have adapted in ways to cope with their effects. In response they have evolved in turn, and keep on doing so. All kinds of environmental factors have affected our evolution, from shifting weather patterns to changing food supplies – even dietary preferences that are largely cultural. It’s as if the whole world is engaged in an intricate, multilevel dance, where we’re all partners, sometimes leading, sometimes following, but always affecting one another’s movements – a global, evolutionary Macarena.

Third, mutation isn’t bad; more to the point, it’s not only good for X-Men. Mutation just means change – when mutations are bad, they don’t survive; when they’re good, they lead to the evolution of a new trait. The system that filters one from the other is natural selection. When a gene mutates in a way that helps an organism survive and reproduce, that gene spreads through the gene pool. When it hurts an organism’s chance of survival or reproduction, it dies out. (Of course, good is a matter of perspective – a mutation that helps bacteria develop antibiotic resistance isn’t good for us, but it is good from the bacteria’s point of view.)

Finally, DNA isn’t destiny – it’s history. Your genetic code doesn’t determine your life. Sure, it shapes it – but exactly how it shapes it will be dramatically different depending on your parents, your environment, and your choices. Your genes are the evolutionary legacy of every organism that came before you, beginning with your parents and winding all the way back to the very beginning. Somewhere in your genetic code is the tale of every plague, every predator, every parasite, and every planetary upheaval your ancestors managed to survive. And every mutation, every change, that helped them better adapt to their circumstances is written there.

The great Irish poet Seamus Heaney wrote that once in a lifetime hope and history can rhyme. Evolution is what happens when history and change are in rhyme.

if there’s fire on the mountain or lightning and storm and a god speaks from the sky. That means someone is hearing the outcry and the birth-cry of new life at its term.

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