About the Author
David B. Agus, MD, author of the New York Times and international bestsellers The End of Illness and A Short Guide to a Long Life, is a professor of medicine and engineering at the University of Southern California and heads USC’s Westside Cancer Center and the Center for Applied Molecular Medicine. He is one of the world’s leading physicians and pioneering biomedical researchers, and is a CBS News contributor. He lives in Beverly Hills, California.
Excerpt. © Reprinted by permission. All rights reserved.
The End of Illness 1
What Is Health?
A New Definition That Changes Everything
Everyone has a vague idea of what it means to live a healthy life. Eating a balanced diet: good. Smoking: bad. Breaking a sweat regularly: good. Binge drinking: bad. Getting a restful night’s sleep: bonus. Being happy: double bonus. Some of us may choose to disregard these basic tenets on occasion, but for the most part, we know the difference between the habits that help us stay youthful and strong, and those that can detract from our well-being.
We try our best to stay out of harm’s way, but what happens when we get sick or develop a chronic medical condition or, heaven forbid, are diagnosed with a serious illness? After experiencing the frustration of Why me? many of us begin to ask ourselves other, more probing inquiries about where we might have gone wrong. Was it something in the water? A lifelong love of hamburgers and fries? An overdemanding boss and, as a result, an overwhelming stress level? Too much alcohol? Too little exercise? Secondhand smoke? Exposure to industrial chemicals? A habit of living dangerously, whatever that might mean? Bad luck?
Or perhaps, some of us think, this outcome was fated because it was just in my DNA all along.
If I could collect a nickel for every time someone in the world thought that genetics was wholly to blame for this illness or that defect, I’d be the wealthiest man on earth. It’s human nature to point fingers at someone or something else for our flaws and shortcomings, and to avoid any personal culpability. Because DNA tends to be a relatively abstract construct, much like black holes or quarks, which we cannot touch, see, or feel, it might as well be a “something else” to which we can assign guilt. After all, DNA is “given” to us by our parents and we have no choice. In this regard, DNA is practically accidental; just as accidents happen, so does DNA, without our having much say in the matter.
What most people don’t think about, though, is that DNA says more about our risk than our fate. It governs probabilities, not necessarily destinies. As my friend and colleague Danny Hillis (whom we’ll meet later when I cover emerging technologies) likes to describe it, DNA is simply a list of parts or ingredients rather than a complete manual that explains how those parts work together to generate results. To hold your DNA responsible for your health is missing the forest for the trees. It’s not the pièce de résistance. I say this knowing full well that DNA does hold certain keys to your health; if it didn’t, then I wouldn’t have cofounded a company that performs genetic testing so you can take preventive measures based on your genomic risk profile. But right from the get-go I want to entice you to start thinking from a broader perspective that goes far beyond your genes. I want you to view your body—from the outer stretches of your skin to the inner sanctum of your cellular makeup—as a whole system. It’s a uniquely organized and highly functioning system that leaves so much to the imagination because we’re only just beginning to solve its riddles.
So therefore, as we probe the mystery of the human body more deeply, we discover that this system, and its complex riddles, don’t necessarily hinge on DNA alone.
The Inescapable Statistics
To understand how we’ve arrived at a place where we focus so much on DNA, and why it’s critical to respect the body as an elaborate system beyond genetics, it helps to explore the evolution of our thinking processes against the backdrop of the challenges we’ve faced—and continue to face—in our quest for health and longevity.
Most of our transformative breakthroughs in medicine have occurred only recently, in the last sixty or so years. Following the discovery of penicillin in 1928, which changed the whole landscape of fighting infections based on the knowledge that they were caused by bacteria, we got good at extending our lives by several years and, in many cases, decades. This was made possible through a constellation of contributing circumstances, including a decline in cigarette smoking, changes in our diets for the better, improvements in diagnostics and medical care, and of course advancements in targeted therapies and drugs such as cholesterol-lowering statins.
Heart disease has been the leading cause of death in the United States since 1921, and stroke has been the third-leading cause since 1938; together, these vascular diseases account for approximately 40 percent of all deaths. Since 1950, however, age-adjusted death rates from cardiovascular disease have declined 60 to 70 percent, representing one of the most important public health achievements of the twentieth century.
Put another way:
But here’s the sobering truth sitting on the sidelines of these triumphs like a lumbering white elephant: the death rate from cancer from 1950 to 2007 (the most current data available from the Centers for Disease Control and Prevention) didn’t change much. We are making enormous progress against other chronic diseases, but little against cancer. Indeed, there are little wins here and there with unique types of cancer. Take, for instance, chronic myelogenous leukemia, a rare type of leukemia that had previously been a death sentence except for a small number of patients who benefited from bone-marrow transplantation. With the FDA approval of Gleevec (brand name for imatinib mesylate) in May 2001—the same month it made the cover of Time magazine as the “magic bullet” to cure cancer—we now have a way to successfully treat most patients and achieve remarkable recovery rates. The drug targets the particular chromosomal rearrangement that is present in this disease (part of chromosome 9 is fused to part of chromosome 22). In clinical trials, the response rate to Gleevec was over 90 percent. People went from their deathbeds to functional life after taking this small molecule with few side effects. But with the more common deadly cancers, including those that ravage the lung, colon, breast, prostate, brain, and so on, we’ve had an embarrassingly small impact on death rates.
Whenever I throw the chart on the previous page, “Change in the US Death Rates by Cause,” on a slide up in front of an audience, I hear a few gasps of disbelief. How can this be? What did we do wrong in our research? Is there a mistake, or perhaps a typo, in this data? I showed this graphic during my 2009 TEDMED talk as part of a larger discussion that included thirty-seven other slides and have received hundreds of e-mails since referring to just this one slide. Many of the inquiries are aggressive in tone—accusing me of being a pessimist and somehow manipulating the data. I wish I could present better news from my camp.
This graph demonstrates the profound effect that therapeutics such as statins have had in heart disease and stroke. Antibiotics and antivirals, including vaccines, have put a major dent in cases of pneumonia and infections. Even when we consider cancer rates across the globe, we can find some statistics that defy all the stereotypes. In some of the sub-Saharan countries, where we tend to think about diseases such as AIDS and other infections common in underdeveloped nations, more people die of cancer than of HIV, tuberculosis, and malaria combined. In 2010, chronic disease overtook infectious disease as the leading killer worldwide. So this problem isn’t just a major cause of concern in America. It affects the global community at large.
The lack of change in the death rate from cancer is truly alarming. The more astonishing observation that I want you to note here, though, is that antibiotics and antivirals do not target the human being—they target the external, invading organism. Statins, on the other hand, target the human system in ways that we are starting to learn more about. Contrary to popular belief, the statins work not just by lowering cholesterol through a single pathway or point of interaction in the body; they have a profound effect on the entire system, lowering inflammation, thereby changing the body’s entire environment. Vaccines also target the system, but do so in a clever way—activating the immune system artificially by making it seem as though a foreign organism has invaded the body.
I stated plainly in the introduction that this isn’t a cancer book, but I need to draw from my experience as an oncologist to get you to understand a few core concepts. We can actually trace our relationship to health to the study of cancer. When we consider the legacy of disease in our history and how we’ve come to understand today a mysterious malady such as cancer, we can begin to see how and why we may have veered off track. We can identify the thinking processes and misconceptions that we’ve blindly embraced and that have thwarted our efforts to advance medicine and, in turn, our individual goals of optimal health. On a positive note, we can begin to see how we can shift direction and embrace a new frontier in the pursuit of health customized to each person, you and me. We can eventually reach a point where we can make meaningful advances in the “war” against all illnesses.
What is cancer? If you have a mass or an abnormal blood test, you’ll likely be referred to a specialist who will stick a needle in you and extract a sample to be examined by a pathologist. Your pathologist (whom you will probably never meet) will look for a certain pattern, because diagnosis today is by pattern recognition. Does it look normal? Or does it look abnormal?
To make an analogy, consider a plastic water bottle as emblematic of a cell. It’s as if your pathologist is looking at a normal plastic bottle and declaring that it’s a normal cell. And then looking at a deformed, crushed plastic bottle and declaring that it’s a cancer cell. That is the state of the art today in diagnosing cancer. There’s no molecular test. There’s no sequencing of genes. There is no fancy examination of the chromosomes. This is how we do it.
A Cancerous Perspective
Cancer, as I explained earlier, is a great metaphor for anything related to sickness. It’s every person’s archenemy, the bearer of all things “bad” when it comes to health, happiness, and of course longevity. All of us fear learning that our body has turned against us—that cancer has struck and the future is uncertain. This uncertainty can be most unpleasant. Suddenly we cannot answer questions such as where, how, why, and when—as in when will I be cancer-free? Or, when will I die?
The most insidious part of cancer is the very nature of this beast: it’s self-generated in the sense that it’s our own cells gone awry. There’s no outside invader. No foreign organism or contagion with a mind of its own and a cellular makeup unlike ours. Cancer is like a sleeping giant lying dormant in all of us. Sometimes, he briefly awakens, inciting a collection of odd cells called a tumor, but, in most cases, before long he’s tamed and lulled back to sleep by the body’s arsenal of artful mechanisms. But occasionally, often when we least expect it, this giant manages to get past our trusty gatekeepers. Something in our defense mechanisms breaks down, throwing off the checks and balances that came so automatically and reliably before, and this causes cellular dysfunction that leads to the growth of cancerous tumors. Cancer presents certain challenges not present in other illnesses, especially those that can easily be blamed on outsiders. Still, the question remains, why can’t we make headway in understanding and combatting cancer, however small and slow?
In 2009, I stood before thousands of colleagues at a meeting of the American Association for Cancer Research in Denver and bluntly said, “We’ve made a mistake.” We’ve all made a mistake, myself included, by focusing down, by reducing the study of disease down to finite points. I proposed that we take a big step back, take a twenty-thousand-foot view of disease. I then made another statement that ruffled a few more feathers in the room: “We don’t necessarily need to understand cancer to control it.” The hisses that I heard leaking from the audience were somewhat disheartening. People evidently got upset, but it was critical to call out where we’d strayed as doctors—and as members of society—because this could help get us back on track. I was as guilty as anyone else in this straying. I didn’t leave this particular audience hanging, though. I knew I had to provide some explanation to justify my statements and offer at least some hope for the future. I then shared how we had grown accustomed to a certain mode of thinking in the sciences that owes its origins to discoveries made a long time ago.
We’ve had a hard time moving past the germ theory of disease, which dominated, and in many ways defined, medicine in the twentieth century. According to this theory, if you can figure out what species of germ you are infected with, then your problem is solved because that tells you how you should treat the disease. This became the general paradigm of medicine. Doctors would perform a laboratory test to determine what the infectious agent was, then apply a treatment that was specific for that agent or class of agents. The treatment only cared about the invading organism, such as the bacterium that causes tuberculosis or the parasite that leads to malaria; it didn’t care to define or understand the host (the human being) or even where the infection was happening in the host. That is why we use the same drug in every patient with a particular infectious disease.
Which is precisely what doctors try to do: identify the disease—diagnose—and treat the diagnosis according to the best-known method. This strategy also allows science to participate because it can objectively test whether a particular treatment is effective when dealing with a given diagnosis. Does quinine help the symptoms of malaria? Is penicillin the best way to treat anthrax? Once science proves what’s best, that’s what the doctors do. Diagnose. Treat. Diagnose. Treat. We, as patients hoping that science makes headway in improving our health, must question these methods and ask ourselves if there’s another, better way—especially for diseases of our system, such as heart disease and cancer, rather than diseases with invading organisms such as the infectious ones.
This scientific approach to medicine is relatively new. Historically, doctors had theories that resembled the traditional Hindu system of ayurvedic medicine, with its emphasis on balances between various forces in the body. Or in the West, a medieval doctor might have tried to make you less “choleric” or more “phlegmatic.” Like Eastern philosophies, the idea was to try to restore the order of the various forces that were controlling the body. But this approach to medicine and honoring the body as a whole was all but abandoned in the early twentieth century, especially in the West, where we became distracted by our triumph over infectious agents. It’s all the more interesting to note that, at the time that the germ theory of disease was really exploding and antibiotics were being discovered, renowned geneticist J. B. S. Haldane articulated the following at Cambridge on February 4, 1923:
The recent history of medicine is as follows. Until about 1870 medicine was largely founded on physiology, or, as the Scotch called it “Institutes of Medicine.” Disease was looked at from the point of view of the patient, as injuries still are. Pasteur’s disc...
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