The Cancer Chronicles Read online

  THIS IS A BORZOI BOOK

  PUBLISHED BY ALFRED A. KNOPF

  Copyright © 2013 by George Johnson

  All rights reserved. Published in the United States by Alfred A. Knopf, a division of Random House LLC, New York, a Penguin Random House Company, and in Canada by Random House of Canada Limited, Toronto.

  www.aaknopf.com

  eBook ISBN: 978-0-385-34971-0

  Hard Cover ISBN: 978-0-307-59514-0

  Knopf, Borzoi Books, and the colophon are registered trademarks of Random House LLC.

  Library of Congress Cataloging-in-Publication Data

  Johnson, George, 1952 Jan. 20-

  The cancer chronicles : unlocking medicine’s deepest mystery / by George Johnson. —First edition.

  pages cm

  Includes bibliographical references and index.

  ISBN 978-0-307-59514-0

  1. Cancer—Etiology—Popular works. I. Title.

  RC268.48.J64 2013

  616.994—dc23 2012048474

  Jacket design by Jason Booher

  v3.1

  For Joe’s girls,

  Jennifer, Joanna, Jessica, and Emmy

  and for his wife, Mary Ann

  * * *

  We must never feel disarmed: nature is immense and complex, but it is not impermeable to intelligence; we must circle around it, pierce and probe it, looking for the opening or making it.

  —PRIMO LEVI, The Periodic Table

  Contents

  Cover

  Title Page

  Copyright

  Dedication

  Author’s Note

  Epigraph

  CHAPTER 1 Jurassic Cancer

  A strange fossil from Colorado … Pathology of dinosaur bones … Monster tumors … The epidemiology of extinction … Cancer in ancient beasts … Tumors in sunflowers … Fish, reptiles, and amphibians…“Why Don’t All Whales Have Cancer?”…A curious law of nature … Contemplating the odds

  CHAPTER 2 Nancy’s Story

  Food pyramidology … Pascal’s wager … Folates, antioxidants, and Finnish smokers … Fruits, vegetables, and giant steaks … Carcinogenic estrogen … The real risks of cigarettes … Emanations from the earth … Cancer clusters … A worrisome lump … Nancy’s cancer

  CHAPTER 3 The Consolations of Anthropology

  In the boneyards of Kenya … Face-to-face with Kanam man…Palaeo-Oncology…Hippocrates and the crabs … The wild beast of cancer … Metastasis in a Scythian king … Skeletons and mummies … Visions of an ancient paradise … Counting up the dead

  CHAPTER 4 Invasion of the Body Snatchers

  “Large and beautifully pellucid cells”…Morbid juices … Seeds and soil … The mysteries of metastasis … A horrifying precision … The ebb and flow of lymph … The surgeon’s diagnosis … Weeds from outer space

  CHAPTER 5 Information Sickness

  Man-made mutations … Funny-looking chromosomes…“A new kind of cell”…Matter that comes alive … The Radium Girls … Coal tar and tumors … Viral invaders … Oncogenes and tumor suppressors … Cellular suicide … Intimations of immortality … A conspiracy of cells

  CHAPTER 6 “How Heart Cells Embrace Their Fate”

  Embryos and tumors … Snail, slug, and twist … Sonic hedgehog … the Pokémon gene … Cyclopean sheep … Holoprosencephaly … 1 + 1 = 3 … Prayers of an agnostic … An endless day at the hospital

  CHAPTER 7 Where Cancer Really Comes From

  The surprising aftermath of Love Canal … What “environment” really means…“The Causes of Cancer”…An environmental turncoat … The carcinogens in coffee … Mitogenesis and mutagenesis … Making sense of the cancer statistics … A maverick presidential report

  CHAPTER 8 “Adriamycin and Posole for Christmas Eve”

  Cancer cells and magnets … The penicillin of cancer … A rare kind of malignancy … Disheartening statistics…“The Median Isn’t the Message”…Flying farolitos … A visit to MD Anderson … Rothko’s brooding chapel

  CHAPTER 9 Deeper into the Cancer Cell

  A physics of cancer … Epigenetic software … The stem cell conundrum … An enormous meeting in Orlando … Espresso and angiogenesis … The news from Oz.…Communing with the microbiome … Beyond the double helix … Dancing at the Cancer Ball

  CHAPTER 10 The Metabolic Mess

  Chimney sweeps and nuns … A “mysterious sympathy”…The case of the missing carcinogens … The rise and fall of vegetables … A mammoth investigation … The insulin-obesity connection…“Wounds that do not heal”…A hundred pounds of sugar … Skewing the energy equation

  CHAPTER 11 Gambling with Radiation

  Flunking the radon test … A ubiquitous carcinogen … Down in the uranium mines … Tourism at Chernobyl … Hiroshima and Nagasaki … Exhuming Curie’s grave … A pocketful of radium … Robot oncologists … Relay for Life

  CHAPTER 12 The Immortal Demon

  A flight to Boston … Stand Up to Cancer … A tale of two cousins … The return of the hedgehog … Where weird drug names come from … Waiting for super trastuzumab … Orphaned cancers … Biological game theory … Contagious cancer

  CHAPTER 13 Beware the Echthroi

  On Microwave Mountain … Cell phones and brain waves … Is cancer here “on purpose”?…Physicists and oncologists … Snapshots of a proteome … Five crazy ideas … Mitochondria and farandolae … Maxwell’s triumphant demon

  EPILOGUE Joe’s Cancer

  Notes

  Index

  A Note About the Author

  Other Books by This Author

  Author’s Note

  Several years ago, for reasons that will become clear in these pages, I was driven to learn everything I could about the science of cancer. How much could I as an outsider, a longtime science writer more com- fortable with the sharp edges of cosmology and physics, grasp of this wet, amorphous, and ever-changing terrain? I imagined the expanse before me as a boundless rain forest whose breadth and diversity could never be captured within a single book or even a single mind. I would find an opening at one of the borders and enter, cutting my own path, exploring where my curiosity led—until I emerged years later at the other side, with a better understanding of what we know and don’t know about cancer. I was in for some remarkable surprises.

  Many people helped along the way. First I thank the scientists who devoted so much time—sitting for interviews, answering e-mails, reviewing parts or all of the manuscript: David Agus, Arthur Aufderheide, Robert Austin, John Baron, José Baselga, Ron Blakey, Timothy Bromage, Dan Chure, Tom Curran, Paul Davies, Amanda Nickles Fader, William Field, Andy Futreal, Rebecca Goldin, Anne Grauer, Mel Greaves, Seymour Grufferman, Brian Henderson, Richard Hill, Daniel Hillis, Elizabeth Jacobs, Scott Kern, Robert Kruszinsky, Mitchell Lazar, Jay Lubin, David Lyden, Franziska Michor, Jeremy Nicholson, Elio Riboli, Kenneth Rothman, Bruce Rothschild, Chris Stringer, Bert Vogelstein, Robert Weinberg, Tim White, and Michael Zimmerman. In addition I consulted more than five hundred papers and books about cancer and sat in on dozens of lectures. Most of these sources are listed as references in my endnotes along with interesting information that didn’t make it into the main text. George Demetri and Margaret Foti kindly allowed me to sit in on a private workshop in Boston organized by the American Association for Cancer Research. Thanks to them and the staff of AACR, including Mark Mendenhall and Jeremy Moore, who welcomed me to the organization’s fascinating annual meeting in Florida. I am also grateful to the Keystone Symposia and the Society for Developmental Biology for accommodating me at some of their events.

  Just as I was getting my boots wet, David Corcoran at The New York Times enthusiastically commissioned and published two of my early reports. Thanks to him and o
ther colleagues—Christie Aschwanden, Siri Carpenter, Jennie Dusheck, Jeanne Erdmann, Dan Fagin, Louisa Gilder, Amy Harmon, Erika Check Hayden, Kendall Powell, Julie Rehmeyer, Lara Santoro, Gary Taubes, and Margaret Wertheim—for their reactions and advice on the manuscript.

  Several recent alumni of the Santa Fe Science Writing Workshop read early versions, offering their good sense and expertise: April Gocha, Cristina Russo, Natalie Webb, Shannon Weiman, and Celerino Abad-Zapatero. Bonnie Lee La Madeleine and Mara Vatz helped with library research and the endless checking of facts. The manuscript was in constant flux and any errors that survive are my own. This will be the seventh book I have done with Jon Segal, my editor at Knopf, and the fourth with Will Sulkin of Jonathan Cape and Bodley Head in London. Thanks to them and their colleagues—including Victoria Pearson, Joey McGarvey, Meghan Houser, and Amy Ryan, a superb copyeditor—and to Esther Newberg, my agent almost from the start.

  Special thanks to Cormac McCarthy, who read an early version of the book, and to Jessica Reed, whose literary sensibility and encouragement were an inspiration. More than once my friend Lisa Chong read through the book sentence by sentence, page by page, helping to apply the finishing touch.

  Finally my deep thanks to Nancy Maret and the family of my brother, Joe Johnson, who allowed me to tell their stories.

  I wonder now, though, if the steady presence of music around me didn’t contribute importantly to my sense of the cancer as a thing with its own rights. Now it sounds a little cracked to describe, but then I often felt that the tumor was as much a part of me as my liver or lungs and could call for its needs of space and food. I only hoped that it wouldn’t need all of me.

  —REYNOLDS PRICE, A Whole New Life

  Tuberculosis used to be called “consumption” because it consumes. It dissolved a lung or bone. But cancer produces. It is a monster of productivity.

  —JOHN GUNTHER, Death Be Not Proud

  Chapter 1

  Jurassic Cancer

  As I crossed a dry, lonesome stretch of the Dinosaur Diamond Prehistoric Highway, I tried to picture what western Colorado—a wilderness of sage-covered mesas and rocky canyons—looked like 150 million years ago, in Late Jurassic time. North America was breaking away from Europe and Asia—all three had formed a primordial supercontinent called Laurasia. The huge land mass, flatter than it is today, was drifting northward a few centimeters per year and was passing like a ship through the waters of what geographers would come to call the Tropic of Cancer. Mile-high Denver was near sea level and lay about as far south as where the Bahamas are today. Though the climate was fairly dry, webs of rivulets connecting shallow lakes and swamps covered part of the land, and vegetation abounded. There were no grasses or flowers—they had yet to evolve—just a weird mix of conifers commingling with ginkgos, tree ferns, cycads, and horsetails. Giant termite nests soared as much as thirty feet high. Splashing and stomping through this Seuss-like world were Stegosaurus, Allosaurus, Brachiosaurus, Barosaurus, Seismosaurus—their bones buried far below me as I made my way from Grand Junction to a town called Dinosaur.

  Occasionally one can glimpse outcroppings of the Jurassic past, exposed by erosion, seismological uplift, or a highway department road cut—colorful bands of sediment that form a paleontological treasure house called the Morrison Formation. I knew what to look for from photographs: crumbling layers of reddish, grayish, purplish, sometimes greenish sediment—geological debris piled up over some 7 million years.

  Just south of the town of Fruita on the Colorado River, I hiked to the top of Dinosaur Hill, stopping for a moment to pick up a pinch of purplish Morrison mudstone that had fallen near the trail. As I rolled it in my fingers it crumbled like dry cookie dough. On the far side of the hill, I came to a shaft where in 1901 a paleontologist named Elmer Riggs extracted 6 tons of bones that had belonged to an Apatosaurus (the proper name for what most of us call a Brontosaurus). Alive and fully hydrated, the 70-foot-long reptile would have weighed 30 tons. Riggs encased the bones in plaster of paris for protection, ferried them across the Colorado on a flat-bottom boat, and then shipped them by train to the Field Museum in Chicago, where they were reassembled and put on display.

  After making my way north to Dinosaur (population 339), where Brontosaurus Boulevard intersects Stegosaurus Freeway, I stood at an overlook and watched Morrison stripes in a canyon reddening with the setting sun. But it was a little farther west, along the Green River in the western reaches of Dinosaur National Monument, that I saw the most beautiful example: a cliffside of greenish grays slumping into purples slumping into browns. It indeed resembled, as the woman at the park headquarters had told me, melted Neapolitan ice cream.

  It was somewhere in these parts that a dinosaur bone was discovered that displays what may be the oldest known case of cancer. After the dinosaur died, whether from the tumor or something else, its organs were eaten by predators or rapidly decomposed. But the skeleton—at least a piece of it—gradually became buried by windblown dirt and sand. Later on, an expanding lake or a meandering stream flowed over the debris, and the stage was set for fossilization. Molecule by molecule minerals in the bones were slowly replaced by minerals dissolved from the water. Tiny cavities were filled and petrified. Several epochs later dinosaurs were long extinct, their world overlaid by lakes and deserts and oceans, but this fossilized bone, encased in sedimentary rock, was preserved and carried through time.

  That hardly ever happened. Most bones disintegrated before they could become fossilized. And of the fraction that survived long enough to petrify, all but a few remain buried. The specimen, now labeled CM 72656 and housed at the Carnegie Museum of Natural History in Pittsburgh, was a survivor. Unearthed by a rushing river or exposed by tectonic forces—somehow it was delivered to the surface of our world where, 150 million years after the animal died, it was discovered by some forgotten rockhound. A cross-section was cut with a rock saw, polished, and after passing through who knows how many human hands, the fossil found its way to a Colorado rock shop where it caught the eye of a doctor who thought he knew a case of bone cancer when he saw one.

  His name was Raymond G. Bunge, a professor of urology at the University of Iowa College of Medicine. In the early 1990s, he telephoned the school’s geology department to ask if someone would come evaluate a few prize specimens in his collection. The call made its way through the switchboard to Brian Witzke, who on a cold autumn day bicycled to the doctor’s house and was presented with an attractive chunk, 5 inches thick, of mineralized dinosaur bone. Viewed head-on, the fossil measured 6.5 by 9.5 inches. Lodged inside its core was an intrusion, now crystallized, that had grown so large it had encroached into the outer bone. Bunge suspected osteosarcoma—he had seen the damage the cancer can do to human skeletons, particularly those of children. Oval in shape and the size of a slightly squashed softball, the tumor had been converted over the millennia into agate.

  The fragment was too small for Witzke to identify the bone type or the species of dinosaur, but he was able to provide a geological diagnosis: The reddish-brown color and the agatized center were clues that it came from the Morrison Formation. Bunge remembered buying the souvenir somewhere in western Colorado—burnished pieces of petrified dinosaur bone were a favorite among collectors—but he couldn’t remember the precise location. He gave the rock to the geologist, asking that he seek an expert opinion.

  Other projects intervened, and so the fossil sat almost forgotten atop a filing cabinet in Witzke’s office, until the day he sent it to Bruce Rothschild, a rheumatologist at the Arthritis Center of Northeast Ohio who had expanded his practice to include dinosaur bone disease. He had never seen a clearer or more ancient example of prehistoric cancer. His next step was to determine just what kind of cancer it was.

  The tumor, it turned out, didn’t exhibit the ill-defined margins or the layered, onion-skin look of an osteosarcoma, the cancer Bunge had suspected, or of another malignancy called Ewing’s sarcoma. Rothschild also felt confident in ruling out myelom
a, a cancer of plasma cells that leaves bone with a “punched out” appearance. The fact that the tumor, gnawing its way outward, had left intact a thin shell of bone was reason to exclude the more invasive multiple myeloma. Every skeletal disease leaves a distinct engraving and, one by one, Rothschild eliminated the possibilities: “the superficial solitary and coalescing pits of leukaemia,” “the expansile, soap bubble appearance of aneurysmal bone cysts,” “the epiphyseal ‘popcorn’ calcifications characteristic of chondroblastomas,” “the ‘ground glass’ appearance of fibrous dysplasia.”

  For an outsider reading Rothschild’s observations, the medical jargon might be somewhere between translucent and opaque, words that gain a grim familiarity only as one strives to understand the sudden disruption of cancer. What is clear from the beginning is the confidence with which a specialist in the obscure discipline of dinosaur pathology can provide a likely diagnosis for a 150-million-year-old tumor. Rothschild went on to rule out the “sclerotic-rimmed lesions of gout,” the “zones of resorption characteristic of tuberculosis,” and the “sclerotic features of gummatous lesions of treponemal disease.” Unicameral bone cysts, enchondromas, osteoblastomas, chondromyoxoid fibromas, osteoid osteoma, eosinophilic granuloma—who would have known that so much can go wrong inside what appears to be solid bone? None of these seemed like candidates. To Rothschild’s eye the lesion had the markings of a metastatic cancer, the deadliest kind—a cancer that had originated from cells elsewhere in the dinosaur’s body and migrated to establish a colony in the skeleton.

  There had been scattered references in the journals to other dinosaur tumors—osteomas (clumps of overeager bone cells outgrowing their rightful bounds) and hemangiomas (abnormal effusions of blood vessels that can form within the spongy tissue inside bone). Like cancer, these benign tumors are a kind of neoplasm (from the Greek for “new growth”)—cells that have learned to elude the body’s checks and balances and exert a will of their own. The cells in a benign tumor are multiplying rather slowly and have not acquired the ability to invade surrounding tissue or to metastasize. They are not necessarily harmless. Occasionally a benign tumor can press dangerously against an organ or blood vessel or secrete destructive hormones. And some can become cancerous. These were rare enough. But sightings of malignant dinosaur tumors were especially scarce. A cauliflower-like growth in the forelimb of an Allosaurus was thought for a while to be a chondrosarcoma. But on close examination Rothschild decided that it was just a healed fracture that had become infected. Bunge’s fossil was the real thing. In a terse, five-hundred-word paper written with Witzke and another colleague and published in The Lancet in 1999, he came to a bold conclusion: “This observation extends recognition of metastatic cancer origins to at least the mid-Mesozoic [the Age of the Dinosaurs], and is the oldest known example from the fossil record.”