The Disease Delusion and the Chronic-Illness Conundrum
You would like Peter. Everyone does. At thirty-six, he is living a picture-perfect existence—married to the love of his life, father of two boys ages six and eight, owner of a lovely home in a suburb everyone always describes as posh, a highly successful software engineer at the top of his profession and at the top of his game. If Peter weren’t such an all-around good guy, it would be easy to resent him. But he is an all-around good guy—bright, caring, gracious, generous, and to all appearances happy and thriving.
Not quite. The outward signs are only part of the story. Behind the trim, fit-looking exterior, Peter suffers from high blood pressure, headaches, and fatigue. He spends his weekends catching up on sleep, when what he really wants to do is participate in activities with his sons and take his wife out on the town. The headaches, he says, come on every afternoon, and by the time Peter arrives home at the end of the day, he feels exhausted.
Of course, he has seen his doctor about all this. The tests showed significantly elevated blood pressure, and the doctor prescribed an antihypertensive medication. When it failed to lower Peter’s blood pressure sufficiently, a second companion medication was prescribed; as the doctor said, “We’ve got to bring down those numbers.”
The numbers came down all right, but the second medication—or the combination of the first and second—brought on erectile dysfunction, and for some time, Peter has been on what he calls “a slippery slope,” trying to find the right combination of drugs to manage his blood pressure and enable him to maintain a vigorous physical relationship with his wife. No luck so far, but the doctor, a guy Peter went to college with, is “sure we’ll find it.” Meanwhile, the headaches, fatigue, and sexual dysfunction continue, and now a pall of depression is settling in as well.
Yet there’s nothing medically wrong with Peter. Other than the blood pressure—definitely something to be dealt with, although not terribly unusual in an ambitious individual in a high-powered environment—he has no health issues. He can’t remember the last time he had a cold. A former varsity athlete in track, he can still run one hundred meters in about twenty seconds. He passed his stress EKG with flying colors, and except for the headaches, he has been a stranger to bodily pain and discomfort—“blessedly,” as he says. So why does he feel so lousy? Why is he plagued with this steady level of low energy, no energy, no hunger to do anything but sleep?
Catherine is sixty-four years old, and you would like her too. Outgoing, funny, even sassy, she just celebrated her fortieth wedding anniversary at a big party thrown by her two children and their spouses and attended by friends, relatives, and her five grandchildren. For more than twenty years Catherine has worked in the financial controller’s office of a large company downtown. It’s a good place to work, with pretty good benefits. Some time ago Catherine opted for a point-of-service health insurance plan: the company pays 20 percent of the premiums, while she pays for the remainder out of her bimonthly paycheck. The plan covers only Catherine’s own needs; her husband, Ted, four years older, is on Medicare.
But Catherine sees doctors frequently. She is bothered by a bit of arthritis in her hands and knees and has slightly elevated blood pressure. She is postmenopausal—like her mother, she went through menopause early—and since her mother suffered from osteoporosis and Catherine herself has what her primary care physician calls “not great” bone density, she is on an osteoporosis management plan.
For these three conditions—arthritis, high blood pressure, osteoporosis—Catherine currently takes six different drugs. She regularly sees a rheumatologist, a cardiologist, and a gynecologist in addition to her primary care physician, and an endocrinologist consults with her gynecologist about her osteoporosis program.
And Catherine feels diminished. Sometimes it’s hard to get up out of a chair. She reminds herself to be careful going down steps. The arthritis comes in painfully sharp episodes that bring her life to a halt. If she gets a flare-up at work, she simply has to stop what she’s doing. She hears herself reciting her ailments to Ted or to friends her own age—and listening to their complaints in turn—and wondering who these old, sick people are.
Yet, like Peter, Catherine is not sick. She has no disease that can be zapped by a drug or cut out of her. And although she is nearly twice Peter’s age, she is not an old woman, either. True, her doctor frequently tells her that her various conditions are simply “part of growing older,” while also advising Catherine to “lose some weight.” She would love to shed five pounds, but she also insists that she is basically a vigorous woman, able to put in ten-, twelve-, even fourteen-hour days when the quarterly financial report is due, and still be ready for a brisk walk with Ted at the drop of a hat, although she’s somewhat slowed down by her deteriorating knees. Now she worries: Will the knees just get worse? Is she looking at surgery up ahead? Are her bones going to break—as her mother’s did? Will the high blood pressure translate into a stroke someday? Will the flare-ups of pain grow worse? Could they become more frequent? Might they become permanent? One doctor tells her to keep moving. Another tells her to take it easy.
Catherine expects to retire in two years, when she will qualify for full Social Security. Ted will retire then too; at the age of seventy, he’ll get the maximum monthly benefit. Both of them have pensions from work and some savings in the bank—not a fortune but enough for the two of them to enjoy what they used to think of as a third age of life. Now they’re not so sure. Catherine wonders if she will spend her third age in doctors’ offices and at the pharmacy, and if she’ll watch her nest egg go for co-pays and supplemental coverage over and above Medicare. Mostly, she wonders if she will grow old stuck in a chair, held there by pain or weakness or fear—or all three.
Granted that you don’t personally know these two likable people. Yet the odds are that you find their situations recognizable, if not familiar. Neither of them belongs in a hospital bed. Neither of them has a disease as such. Neither of them is unable to carry out most of life’s responsibilities and pleasures, although both are somewhat limited in doing some things. That’s it, really: they are limited. And there’s no real end in sight. What’s going on?
We all know that we’re living longer—that’s certainly good news. The bad news, however, is that we don’t seem to be doing the longer living very well. Far too many of us spend far too much of our longer lives like Peter and Catherine—not wholly sick but not wholly well. Rather, we’re suspended between the two states, between good days when everything feels okay and bad days when nothing does. It’s a difference that’s hard to split; the limitation is always potentially there. It hovers over us, disabling or debilitating us physically, mentally, emotionally.
Chronic diseases—those persistent or recurring illnesses or conditions that don’t go away and that in fact grow progressively worse—are keeping us from enjoying our extended longevity to the fullest. When these diseases are not killing us before our time, they are burdening our lives with pain, discomfort, or limitations that undermine the living of life and rob us of the quality of life.
And the incidence of such illnesses seems to be on the rise. Look around. People are either on meds like Peter, or excusing themselves from an activity as Catherine occasionally feels she must do, or complaining endlessly because of their arthritis, asthma, high blood pressure, acid reflux, gout, fibromyalgia, or chronic fatigue syndrome. Or so it seems.
In fact, chronic illness is becoming more prevalent—and at an ever faster rate. The quarter century from 1985 to 2010 saw dramatic increases in the number of people diagnosed with diabetes, cardiovascular disease, and chronic obstructive pulmonary disease. More people suffered strokes and depression. More of us experienced bone loss from osteoporosis, failure of muscle strength, kidney and liver ailments, and macular degeneration and degraded vision. The incidence of autism in children and dementia in adults increased alarmingly. Today, almost half of adult Americans—133 million of us—suffer from at least one chronic illness. Among Medicare beneficiaries sixty-five and older, the statistics are worse: more than half are being treated for multiple chronic conditions—diabetes and hypertension and heart disease, to take one common example.
It all comes at a high price. The Centers for Disease Control (CDC) estimate that managing these illnesses accounts for some 78 percent of the nation’s health expenditures. Health-care spending for a person with one chronic condition is almost three times greater than spending for someone without a chronic condition. Spending is seventeen times greater for someone with five or more conditions. A 2011 study by the World Economic Forum projects that by the year 2030, the cost of chronic illness treatment worldwide will exceed $47 trillion. That represents the kind of economic impact that can bring countries to their knees.
In addition to what we spend, there’s what we lose. Chronic diseases are the main cause of absenteeism from work and of lowered productivity on the job. The CDC ascribes seven out of ten American deaths to chronic diseases, with heart disease, cancer, and stroke accounting for more than half of all deaths each year. Worldwide—for this is a global epidemic—these illnesses rob us of more years of life than all the infectious diseases combined everywhere, except in sub-Saharan Africa.
But of course, the cost to the individual sufferer is ultimately immeasurable. How do you quantify that burden—the pain, discomfort, encroaching disability and dysfunction, the shame of feeling yourself a burden to those you love, the sorrow of losing the quality of your life?
Actually, a study published at the end of 2012 tried to do that very thing, examining diseases attributable to sixty-seven risk factors in order to define what it called the global burden of disease. The study, covering the years 1990 to 2010, used a measure called the disability-adjusted life year, or DALY. The DALY combines the years of life lost because of premature mortality and the years lost because they were lived in a state of subpar health, both due to these risk factors. The study results paint a startling new picture of the nature of disease globally.
For so much of world history, the burden of disease was to be found in the risks of infectious diseases in children, which caused rampant infant mortality and early childhood deaths. Now, the study showed, the risks are at the other end of life—in what the study called the “years lived with chronic disease.” These are the non-infectious diseases that put a brake on living, sapping an individual’s vitality on the way to his or her premature death. Indeed, the dramatic reduction in mortality among infants and children under the age of six—grounds for celebration and gratitude—has been answered by an even more dramatic rise in mortality from chronic illness. If you’re looking for the health headline for our time, this is it.
The study also told us why the rise has been so dramatic—not that we didn’t already know. It’s the way we live. In the twenty-year period the study covered, from 1990 to 2010, the greatest increase in disability—that is, in limiting our lives—came from heart disease, stroke, depression, and metabolic diseases like diabetes, all of them directly related to environment, diet, and such lifestyle behaviors as exercise. Ischemic heart disease, as it is called—that is, heart disease due to hardened arteries that reduce the blood supply to the heart—which was the fourth-ranked disability in 1990, rose a whopping 29 percent to assume the dubious top rank by 2010, while the incidence of stroke increased 19 percent and depression 37 percent. Diabetes, meanwhile, has become a global epidemic, with China and India at the epicenter of its growth. These are the afflictions of our era, and they are killing us slowly.
Whereas our forebears were bedeviled by contagions that science has now virtually put an end to, we are plagued by illnesses we have to battle constantly. It means that where health and well-being are concerned, we are in a whole new ball game, and we confront a whole new set of challenges. That is the conundrum of chronic illness.
It is a dilemma with many horns. The challenges we confront touch upon the health infrastructure and delivery system; our current medical strategy for treating chronic illness and the training and education of those who execute the strategy; even our understanding of chronic illness, of its origins and causes, and of the individual’s role in addressing it. It’s a lot to deal with.
THE GLOBAL HEALTH SYSTEM
It is axiomatic that this rising burden of chronic illness sets up a very direct set of challenges to health-care systems around the world. The problem is that our health-care systems are in no way ready for the challenges.
Yes, we have now a sophisticated medical infrastructure, honed to the sharpness of a weapon, to address infectious diseases and acute care. You go to a doctor’s office or enter a hospital or clinic sick or injured, and you exit cured—your body stitched together, your malady diagnosed, prescription in hand. Everything about the infrastructure—the training of physicians and other health professionals, therapeutic processes and procedures, hospital and clinic organization, not to mention insurance and reimbursement—is geared to curing a contagious illness that derives from a single cause or remediating an acute injury or medical event like a heart attack or stroke. Unfortunately, this pill-for-an-ill system is in no way suited to addressing the chronic illnesses that are today’s health reality.
Neither is the clinical education of the physicians and other health-care professionals charged with delivering and administering cure and care. Medical schools in the United States and around the world do a superb job training physicians to be experts in crisis care, but they offer little education in how to manage chronic illness. This disconnect is measurable: The management of chronic illness constitutes nearly 80 percent of our health-care expenditures but occupies close to zero time in the training of physicians.
What’s more, our current approach to chronic illness—palliating its effects, episode by episode—mandates a different paradigm of health-care delivery from the one we now have, the paradigm developed to provide acute care in a crisis. Lacking a single, easily identifiable beginning and end, chronic illness as we now deal with it will require long-term management—actually, self-management by the patients themselves. Yet today’s health-care infrastructure, geared to the acute care of infectious illness or health emergency, just isn’t set up for that. It doesn’t have the tools such long-term self-management demands as an absolute prerequisite of success. Granted, many medical schools have begun to think in fresh ways about training and to make changes in both course work and practicum experience. And there are some schools—notably, Bastyr University in Seattle, Washington—that are dedicated to the kind of medicine that is clinically applicable to the management of chronic illness. (Full disclosure: I was a founding trustee of and professor at Bastyr.) These developments are very welcome, yet they serve to etch in even sharper relief the disconnect between the health care we have and the health care we need.
THE DISCONNECT
At the heart of the disconnect is the fundamental medical fact that an infectious disease can be traced to a single cause or agent. That fact became the basis of a now well-defined process for developing drugs that could address the identifiable cause or agent and thus cure the disease. It also gave rise to the now humongous pharmaceutical industry that carries out the process.
Remember high school biology and learning about all those metabolic processes going on in our bodies—the zillions of biochemical reactions happening all the time within our cells, step by step by step? Put very simply, think of a disease as caused by an overly active step in one of the metabolic processes going on in the body—a single step that has gone out of sync or out of control. If you can find or create a substance that will interfere with that overly active step—block it, inhibit it, alter it in some way—you more or less transform the effect of the disease and reduce its symptoms. That’s precisely what drugs do.
Back in the day—it’s worth remembering that the therapeutic use of antibiotics dates only to 1940—drugs were made from natural sources like medicinal plants or, in the case of antibiotics like penicillin, which was derived from a naturally occurring blue mold, were the products of bacterial and fungal metabolism. These naturally derived compounds were pitted against the specific metabolic process known as cell wall synthesis, a process unique to the bacteria that cause infectious diseases; tellingly, the process was not found in animal cells. This lucky distinction between bacterial and human cell metabolism made the antibiotics both safe to use and highly selective in their action—naturally so. And they did just what the doctor ordered: They literally altered the cause of the illness, more or less morphing it out of existence.
Flushed with success, particularly given the role antibiotics played in saving lives on the battlefields of World War II, the pharmaceutical industry turned its attention to realms beyond infectious disease—to the kinds of infirmities suffered by those diagnosed with chronic illnesses. For these illnesses, scientists knew they would not find a specific bug causing a specific infection. Instead, their aim was to identify the particular biological process related to the dominant symptom of the particular chronic illness—whether pain or inflammation or a specific misstep in a metabolic activity associated with the disease—so they could then develop a drug that would modify the effects of this process, blocking or altering the misstep in the complex web of metabolism.
A different kind of development process evolved to create these drugs, and it profoundly reshaped the pharmaceutical industry. The process begins with what is known as high-throughput screening, in which chemists evaluate exactly how tens of thousands of chemicals synthesized in the lab influence the metabolic activity being targeted. The smaller the amount of chemical required to interfere with a particular step in the metabolic process, the more active the chemical is considered to be—and the more effective the drug. Next, those compounds identified as most active are screened for safety across a range of different models. A substance showing both high activity and acceptable safety in this screening is then tested in humans, and if it passes those tests, it goes onto the market. That is, your doctor can prescribe it to you as a short-term therapy to cure an acute illness caused by the specific misstep in a particular metabolic process for which the drug was developed.
And where chronic illness is concerned, there’s the rub. For today’s rising burden of chronic illness cannot be attributed to alteration in a single step in the complex metabolic web. Rather, the diseases and conditions we call chronic derive from a variety of causes, each expressed in its own symptom or set of symptoms. And because the drugs for the illnesses treat only the dominant symptoms—that is, the effects, not the ultimate cause—you don’t really get over a chronic illness, no matter how often you pelt it with drugs or how many kinds of drugs you pelt it with. Instead, it either persists or recurs; in fact, it actually gets worse over time. The outcome of the treatment isn’t a return to good health but rather increasing disability and a diminished quality of life.
You see what the problem is. You tell your doctor you feel tired and you sort of ache all over. Pressed for specific details, you report that you haven’t been sleeping well, can’t concentrate, have no energy, and just feel wiped out. Trained in a pharmaceutical strategy that seeks one cause to explain one disease that can be treated with one drug, the doctor is stymied at best; how can he or she help you, the poor suffering patient?
Eager to alleviate your multiple symptoms, your doctor typically prescribes multiple drugs. What else is a doctor to do? There is no drug for the specific cause of the patient’s complaints—for the reason that the cause, which is complex and multifaceted, doesn’t lend itself to being cured by a single drug. But thanks to a booming pharmaceutical industry, there are lots of drugs for the various symptoms. So, for example, a patient with type 2 diabetes might be prescribed one drug to treat the fatigue she feels, another to suppress her appetite, something else to deal with the headaches, and yet another treatment for her blurred vision. Someone with arthritis might take a range of anti-inflammatory medications in combination with painkillers to alleviate the discomfort. Unlike antibiotics that address the cause of a specific infectious disease, the therapies prescribed for these chronic illness sufferers treat the effects of their disease, not its multiple causes.
It’s called polypharmacy—simultaneously taking a number of different drugs to treat a range of symptoms of an ailment. Of course, if you suffer from more than one ailment—from diabetes and arthritis, for example—the polypharmacy multiplies even further. It’s why Catherine is taking six drugs for her three recognizable complaints; her well-meaning doctors are stemming the impact of her arthritis, cardiovascular weakness, and possible osteoporosis—camouflaging them to a sufficient extent that she can get on with her life—without ever tackling the origins of the impacts.
What happens as a result? One outcome is that the disease or diseases will continue to progress over time. As this happens, the symptoms become more severe and more medications are required to alleviate them. In effect, these patients become lifetime consumers of medications that were expressly designed—and approved by regulators—to be used for a limited time only so they could get on with their lives.
But so far from getting on with their lives, patients may actually be undermining their lives as they continue to take the medications, for they become increasingly susceptible to adverse drug reactions. “Adverse reaction” may sound like a minor irritation, but in fact, ADRs are a leading cause of death in the United States. Remember Vioxx, the anti-arthritis drug pulled from the market when it was implicated in potentially tens of thousands of deaths? And Avandia, the antidiabetic implicated in heart attacks and left on the market only under the most stringent restrictions?
Perhaps the most striking example of all was that uncovered by the Women’s Health Initiative study, initiated by the National Institutes of Health in 1991, on the use of hormone replacement therapy, HRT, to treat the ill effects of menopause. It had been assumed for more than fifty years that the use of estrogens and synthetic progesterone replacement therapy by menopausal women was good for their bones, breast health, heart, and brain as well as being a salve that could assuage night sweats, hot flashes, and the mood swings and depressive symptoms associated with the onset of menopause. Millions of women took this combination of drugs for several decades, quite naturally assuming that the drugs had been thoroughly tested and found to be safe for long-term use.
Their assumption was wrong. No long-term outcome studies had ever been done on HRT until the Women’s Health Initiative study, the results of which were so alarming that the study directors felt morally bound to announce them early, before all the data were in. The study found that for many women, the particular combination of equine estrogens (Premarin, from pregnant mares) and synthetic progesterone not only did not improve heart and brain function but actually increased the risk of both heart disease and dementia.
How could this happen? Vioxx, Avandia, and the Premarin-progesterone combination had all passed rigorous safety testing in different assays and in animal models, not to mention undergoing a range of human tests in double-blind, placebo-controlled trials to receive the seal of approval of the Food and Drug Administration. How can drugs that have passed muster in the toughest safety tests on earth turn out to be so tragically unsafe?
I have alluded to one reason already: the safety testing is based on the use of these drugs for a limited duration, not for the course of a lifetime. What appears safe in a short-term study may, over the long term, begin to show very different effects, especially when the drug is taken by so many different people with very different genetic profiles, different lifestyles, and different causes of their disease. It looks very much as if a law of unintended consequences may apply to any drug used by many people over many more years than the studies evaluated in the approval process.
There’s another possible reason for ADRs. Remember how drugs work: they interfere with—they block or inhibit—certain overly active metabolic steps associated with the symptoms of the disease. Anti-inflammatory drugs, for example, inhibit the effects of key enzymes that cause tissue to swell and send alarm signals to your brain. Anti-ulcer drugs block the production of stomach acid. Drugs that treat high blood pressure either block the hormones that regulate the complex process for controlling blood pressure or prevent their release. Drugs that treat depression inhibit the normal regulation of certain neurotransmitters in the brain. The problem is that the specific biological target a drug blocks because it is related to a disease state in one place in the body may be important for normal functioning in other places within the body. To put it very simplistically, the inflammation that is causing symptoms of severe pain because it is out of control over here in one part of the body is a normal, essential housekeeping process over there in another part of the body. Obviously, if a patient continues to take an anti-inflammatory drug over a long period of time, that can adversely affect the “distant” normal housekeeping and induce a dangerous situation seemingly unrelated to the original problem.
That is indeed what happens. As with Peter, your blood pressure may be going down, but keeping it down knocks out your sexual potency. Your ulcer may be under control, thanks to your antiulcer drug, but it may be causing anemia. Or your arthritis pain may now be manageable due to the powerful anti-inflammatories you’re taking, but those same anti-inflammatories may be contributing to your risk for kidney disease. And who knows what other impacts blocking those specific enzymes may have elsewhere in your body’s systems? In fact, in many cases, we know all too well. It is why your doctor tells you to go easy on over-the-counter ibuprofen or naproxen, not to mention acetaminophen. Long-term use of the former can lead to gastric bleeding, heart attack, and stroke, while the excessive use of the analgesic acetaminophen can damage the liver irreversibly.
This does not mean that there is no value in taking specific medications to manage the symptoms of chronic illness. It suggests, however, that it is best to use fewer medications, at the lowest dose able to manage the condition, and for the shortest time possible. It also means that the disease is very likely still there—and getting worse.
ACCEPTING THE INEVITABLE?
So there’s the dilemma—part of the dilemma anyway. We have a health-care system equipped and ready to cure the occasional acute disease, and our health-care horizon is packed with the chronic suffering of people like Peter and Catherine. The short-term drugs being applied as a long-term remedy to this suffering hold the potential for scary adverse impacts and treat only the effects of an ailment, which continues to progress in severity over time. Our health system and the understanding of disease on which it is based aren’t working for the health reality of today, which is chronic illness.
Yet the most commonly voiced response to this dilemma is that it is inevitable. The longer we live, the more chronic ailments we will get and the more severe they will become as we age. Accept it.
Well, no. Not if we don’t have to. And we don’t.
Let me tell you about my great-grandfather. He pursued a number of careers in his life of ninety-six years: dentist, jeweler, rancher, antiques dealer, and, in a kind of near-career, marathon canasta player. He was married to my great-grandmother for sixty-five years, and after her death, he enjoyed a fifteen-year relationship with a woman he traveled seventy miles by bus to visit. On Thanksgiving of his ninety-sixth year, after six hours of playing cards with his children, grandchildren, and great-grandchildren, he announced that having seen us all grow up, and having outlived two wonderful women partners, he would be moving on soon, and he wanted us to know that. Two weeks later, he died in his sleep.
That some of his physical powers had diminished somewhat in his last years was undeniable, but he never lost his zest for living and never stopped reaping the joy of life. He had no reason to; he wasn’t sick or infirm or particularly disabled in body, mind, or spirit. It seemed to me he lived the maximum life span at the optimum level of health and well-being that his genetic potential enabled. Wouldn’t it be great if everybody could?
Everybody can. And they can for a reason articulated most succinctly and powerfully, in my view, by Dr. James Fries, a professor of medicine at the Stanford University School of Medicine. Very early on in his career, Fries became interested in the question of why people get more chronic illnesses as they age, especially since there is no evidence that aging in and of itself is the cause of any disease. In a watershed 1980 paper in the New England Journal of Medicine, Fries described the reserve of function in the body’s organs that, in youth, is well above what is needed for average everyday living. It’s like a savings account of extra biological capability that we can draw on when we need to—say, when we confront trauma, injury, or illness. At a moment of stress, for example, the heart and lungs can increase their response three to four times above what is needed for functioning at rest. Once the stress is over, both organ functions return to normal baseline with no adverse consequences.
This is true for every organ system, by the way—for liver function and its ability to let us tolerate toxins, drugs, and alcohol; for kidney function and its ability to control blood pressure; for muscle function as it relates to endurance; for immune function and our resistance to infection; for brain function as it relates to memory and cognitive function. Each system has its own reserve that equips it to bounce back from an exceptional response to an exceptional need.
As we age, however, we lose organ reserve. There’s simply less in the account—less for Catherine than for Peter—which means there is diminished function to draw on in times of need and less ability of the organ to bounce back. The rate of speed at which we lose this reserve is what more or less shapes our individual process of biological aging, and it has been well proved that people lose organ reserve at different rates and therefore age differently. We all know fifty-year-olds who are biologically seventy. They feel old, look old, act old. And it’s true: based on their loss of organ reserve, they are old. It is also possible to be chronologically seventy with the biological age of the average fifty-year-old; we probably know people like that as well—although we may not like them very much.
What Fries taught us in his paper, however, is that our biological age is correlated with our individual risk of chronic illness. While our average life expectancy has nearly doubled over the course of a century, we are spending a lot of that extended life span at risk for chronic illness or disabled by it. In other words, we spend a lot of that time drawing down, using up, and thereby losing organ reserve, thus speeding up our own biological aging.
So if we could reduce the loss of organ reserve as we grow older, thus slowing our biological aging and, since the two are correlated, the amount of unnecessary chronic illness we experience, we could not just increase average life expectancy but also lengthen our time of vigor and shorten our time of infirmity or disability. Fries used the phrase “compression of morbidity.” He meant we could squeeze down the time between the onset of disability and the moment of death by lengthening the time before the onset of disability. We could, in short, stay younger longer.
How do we do it? Fries’s idea was to make it happen by implementing the particular lifestyle behaviors and ensuring the particular kind of environment that would enable the individual to retain organ reserve as long as possible. It’s the way we live, in other words, that can maximize our time of vigor and compress the period of chronic illness and senescence to a very short period at the end of life.
When Fries first postulated in 1980 that lifestyle and environment could minimize the rate of loss of organ reserve and compress morbidity, he received no small amount of criticism on the grounds that he had no “proof” for the hypothesis. Eighteen years later, he offered the proof. His 1998 follow-up article in the New England Journal of Medicine showed the results of a study of 1,741 university alumni. They underwent baseline health surveys in 1962 when their average age was forty-three and were then examined annually starting in 1986. The results of the study confirmed Fries’s hypothesis: those university alums showing high-risk lifestyle behavior and environment at the baseline in 1962 and at the first annual checkup in 1986 experienced twice the cumulative disability—the biological aging—of those with low risk. For the latter, lower-risk group, the onset of the first disability was postponed more than five years beyond the onset of infirmity experienced by those showing greater health risks in their forties. That’s a lot of years. And it confirms that it isn’t your chronological age but your biological age that counts.
GENETIC INHERITANCE
Well, I hear you saying, but what about genes? Your DNA is your DNA, and you can’t fight your genetic inheritance. No, you can’t, but “inherited” does not mean “inevitable.” Certainly, genes are important in influencing our health, but there is simply no such thing as chronic-disease genes, as was once generally assumed. What we have are genes that encode our uniqueness in how we respond to the circumstances of our environment and to our own individual behaviors.
The term for it is “genetic expression.” Our genes get messages from our interactions with our environment and with how we choose to behave, and they translate those messages into cellular instructions; these instructions are what then control our health and disease patterns. You might say our environment and our behaviors talk to our genes, and what they say can change the way our book of life is read in the process of genetic expression—that is, through the translation our genes make.
What does it mean? For one thing, it means we are not hardwired to come down with the diseases that undermined the later years of our parents or grandparents. Your mother and father both gasped their way through an asthmatic old age and you figure you will too? Not if that gene encoded for asthma gets a totally different message. Your doctor tells you you’re in danger of succumbing to the hereditary heart disease that killed your father? You have time to deactivate that fatal legacy by changing the messages your genes receive. Catherine is not doomed to become a brittle-boned old lady just because that’s what happened to her mother. She can make changes to her lifestyle, her diet, and her exercise habits and thereby bring the needle back from osteoporosis.
Do you know about the BRCA gene, the feared mutation that prompts so many women found to possess it to submit to radical double mastectomy to save their lives? It is actually a prime example of this reality about changing the message our genes receive. Before 1940, the incidence of breast cancer developing in women with the BRCA mutation was 24 percent. By 2013, the incidence was greater than 85 percent. What changed to cause that extraordinary leap in the occurrence of the disease from this mutation? Not the gene; genes can’t and don’t change. It was the environment influencing the gene’s expression that changed: diet, exercise, other lifestyle behaviors. Alter the environment and you alter the way genes express themselves in response—and the health outcome. It all depends on the message the gene receives.
The bottom line is that genetic inheritance is not fate. Your lifetime health was not predetermined at your conception. On the contrary: you have the opportunity—and the power—to shape your own pattern of health and longevity. It’s what personalized health management is all about.
A NEW MODEL—AND A PIONEER WITH PROOF
So chronic illness, the rising global burden that our current health systems are inadequately equipped to address, is not the inevitable circumstance of old age or the predetermined outcome of our genetic history. Rather, it occurs at the intersection of the information encoded in our genes and the messages transmitted to our genes from our environment and our behavior. This is a revolutionary change in our understanding of the origins and causes of the chronic ailments that afflict so many of us. It is forcing us to take a revolutionary approach to the way we treat these diseases. Clearly, our health as we grow older is much more under our control than previously assumed. The information encoded in our genes doesn’t tell us how we are going to get sick; it enlightens us about how we should live to maximize our health over a longer life span.
We need a new health model to deal with that fact, and fortunately, one is emerging. Based on the realization that genes don’t cause chronic illness and most drugs don’t cure them, it is providing clinical proof that when we address chronic illness through environmental and lifestyle factors, positive health outcomes result.
The person who really brought this to everyone’s attention is Dr. Dean Ornish. I first met Dr. Ornish in 1982 in San Francisco; I had taken a sabbatical from teaching to become a research director at the Linus Pauling Institute of Science and Medicine in Palo Alto. Some years before, Dr. Ornish had initiated his landmark clinical study of people diagnosed with—some of them suffering quite substantially from—existing cardiovascular disease. The study went on for five years—sufficient time to produce truly reliable results. Participants agreed to eat a diet of minimally processed whole grains, vegetables, fruits, and low-fat animal products, and to practice stress reduction exercises and yoga. A matched control group would not follow these behaviors. Because so many of the study participants had serious heart problems, the program regimen was considered by many to pose a very high risk. Of course, Dr. Ornish and his team were aware of the risks and were prepared for the challenges of administering the study. Detractors—and there were a number of them within the world of medicine—nevertheless felt that the study would at best produce ambiguous results and at worst do harm to the participants.
The results, published in the 1990s, proved all the detractors dead wrong. Using the sophisticated diagnostic tool known as positron emission tomography (PET), which measures the amount of plaque in the major arteries that serve the heart, the Ornish program resulted in modest regression of existing plaque after five years of participation in the program, whereas the matched group of patients who did not engage in the program experienced progression of their disease over the same period of time. A follow-up study three years later reported a relative reduction of nearly 8 percent in the amount of plaque in the arteries of the group complying with the program versus a nearly 12 percent average worsening of plaque in the group of nonparticipating matched patients. The Ornish group’s conclusion was simply put: “More regression of coronary atherosclerosis occurred after five years than after one year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.”
It was a groundbreaking study—in the way it was designed and executed, in its duration, and of course in its impressive results. It put to rest the long-standing criticism that no well-controlled clinical trial offered data to support the hypothesis that an aggressive intervention in lifestyle and nutrition could have a positive influence on heart health in people with the disease.* On the contrary. The Ornish study showed that changing lifestyle behaviors improved health and maintaining the changed behavior improved health even more. In essence, it proved the role of lifestyle and environment in determining genetic expression and influencing health status. How do we know that’s what it proved? I’ll put it this way: there’s an app for that.
ASSESSING HEALTH STATUS: BIOMARKERS
What do I mean when I use the word “health”? One answer is that it’s biological age. More generally, it is a state of optimal physical and physiological function—the maximum functional organ reserve possible at any particular time. The good news is that today’s medical technologies provide us with important new tools for measuring function and therefore for assessing not just the absence of disease but the presence of health.
For example, did your last annual checkup include an electrocardiogram: an EKG? If so, that display of your heartbeat provides a good check for the presence of heart disease. But it is possible to have a normal heartbeat as recorded in an EKG, get a clean bill of heart health from your doctor, and suffer a heart attack on the way out of the doctor’s office. It has happened—more than once.
That is why doctors often use another tool in addition to the EKG—the cardiac stress test. You hop up on the treadmill and walk or jog or run while the treadmill moves at different speeds and is inclined upward and downward to different grades of steepness. This challenges the heart, and the testing technology can then measure its ability and the ability of the blood vessels to accommodate the increased demands put upon them. The result is much closer to a measurement of the biological age of the organs than what a resting EKG test can provide.
Something similar is used in testing for diabetes. The standard test measures the amount of glucose in the blood after an overnight fast; an elevated level is a hallmark of the disease. But it is possible for a person in the early stages of diabetes to produce a normal result on the fasting blood sugar test. A more telling measure is to determine how well the body can metabolize glucose; this can be done through an oral glucose tolerance test (OGTT). Like the cardiac stress test, the OGTT is a challenge that can help measure organ reserve. The subject drinks a solution containing a specified amount of sugar. The level of glucose in the subject’s blood is then monitored periodically over the next three to six hours. During this time, of course, the stress of the sugar load is challenging the subject’s ability to properly metabolize it. Difficulty in handling the load—in metabolizing the sugar—will indicate a reduced organ reserve, and the test will read as abnormal. Yet it is not unusual for a person with a normal fasting blood glucose level to have an abnormal OGTT.
This ability to evaluate the actual functional reserve is crucial to curing chronic illness. Chronic conditions, after all, start with subtle changes in function that can precede the diagnosis of a disease by decades. If there were some way to assess these subtle functional changes early—before a disease develops—we would be able to monitor and track our functional health status. There is a way—through biomarkers—and it is fueling a major shake-up in medicine.
Biomarkers are indicators of our functional health status. They reflect how our genes are being expressed in terms of our own unique lifestyle and the various conditions and circumstances to which our personal environment exposes us. Blood pressure, percentage of body fat, the level of glucose or triglycerides or cholesterol in our blood, the way that cholesterol is packaged in LDL or HDL forms: these are just some of the more common biomarkers, all of them signals that indicate how our genes are being translated into physiological, physical, and mental functions—gauges of our genetic expression. When we undergo stress, get an infection, eat nothing but supersized junk foods on vacation, confront trauma, or are exposed to toxins, our genetic expression changes in response. Of course it does: our environmental circumstances are disrupted, so our interactions with the environment necessarily change in response, and the message to our genes is different from the message they would receive when our bodies are in a state of peace. The change in genetic expression also shifts the pattern of biomarkers, and the shift in turn indicates that our health status is disturbed in response to the present environment. But because we each possess different genetic information, we will each experience disturbances in our health status in a different way.
Let’s say your genes are stimulated by the threat of an infection floating around in your environment—a cold or flu, for example. Your genetic expression shifts into gear, mobilizing your body’s response to that threat by activating your immune system. In the short term, this response is highly beneficial: you avoid getting sick or you get less sick than you might. But over the longer term, such a change in genetic expression can turn what was beneficial into something downright injurious to the specific tissues and cell functioning that keep getting involved. That injury is what we call chronic illness.
It means, among other things, that chronic illness isn’t something you “contract,” the word we tend to use for getting an illness; you don’t catch a chronic illness the way a fielder in baseball nabs a line drive smack into the pocket of his glove.
In the purest sense of the word, in fact, there are no real diseases. This is why I say disease is a delusion. Rather, the individual’s unique genetic makeup responding over time to a perceived threat alters the functioning of specific tissues, and that “injury,” like a banked fire that burns slowly, becomes a sustained, low-grade impairment. We call it a disease or illness, and if it goes on for a while, we call it a chronic illness. But it’s really our genes responding to messages from our diet, our environment, and our lifestyle behaviors. Through their changing levels in the body, biomarkers show us just how the genes are responding to specific environmental threats.
But here’s the headline. In addition to the many well-known examples of biomarkers—cholesterol, blood pressure, triglycerides, or glucose in the blood—there are also literally hundreds of new biomarker candidates that can help to pinpoint changes in a person’s health well before disease develops. There’s a biomarker for assessing a woman’s risk for uterine cancer using the Pap test. The prostate-specific antigen (PSA) biomarker test evaluates a man’s risk of prostate cancer,* while the levels of hemoglobin A1c in the blood as a marker for diabetes have become routine over the past twenty years. One of the new biomarkers in the blood that we’ll meet again later is high-sensitivity C-reactive protein: hs-CRP. This biomarker is an indicator of chronic inflammation and, especially when combined with a companion biomarker in the blood, homocysteine, can alert us to a person’s early risk of heart disease, arthritis, diabetes, or dementia, four of the five major chronic illnesses.
What is crucially important, of course, is that these biomarkers are the smoke signaling the fire of altered health status and suggesting there just may be a chronic illness lurking up ahead. Sniffed out early enough, they provide time to take steps to avert the potential chronic illness or alter its progression.
There are, to be sure, certain factors in the environment—like a famine or an infectious epidemic—that send such a strong message to the genes that everyone’s health is affected, regardless of genetic history, and biomarkers will record the fact. But with most of the environmental factors and lifestyle behaviors we experience on a daily basis—like smoking or eating a diet high in saturated fats—the influence on genetic expression will vary from person to person.
What the Ornish study demonstrated was that biomarkers register the shifts in an individual’s genetic expression as the individual’s environmental factors and lifestyle behaviors change. In those participants who followed the program and changed their diet and exercise levels, the biomarkers signaled improved heart function; in those who did not follow the program, the biomarkers of heart disease were still there and the heart function of those people regressed. Among other implications, this means that biomarkers are the key to shaping the kind of personalized approach to curing chronic illness that this book is about.
The Ornish study is foundational to the development of today’s emerging new approach to the management of chronic illness, and Dean Ornish himself is one of the principal pioneers of this burgeoning revolution in lifestyle medicine. Whether they’re aware of it or not, millions of people down the generations will have reason to be grateful to him.
THE PERSONAL TOUCH
The Ornish study offered proof of the gene-environment connection to chronic illness. Since the study, there have been considerable additional advances in understanding how the connection applies to those chronic illnesses that together account for the bulk of health-care expenditures today—heart disease, arthritis, dementia, cancer, and type 2 diabetes—as well as the common secondary effects of type 2 diabetes: chronic kidney disease, stroke, liver disease, neuropathy, and loss of eyesight.
So we can say there has been progress indeed in our understanding of the chronic-illness conundrum—the essential first step in changing our approach to dealing with the rising global burden of chronic illness. One final challenge remains, however, and that is the recognition that in order to maximize the health outcomes of any new approach, it must be individualized—that is, personalized to the health status and specific health profile of the individual and, in great measure, managed by the individual over the long haul.
Why are a personalized approach and individualized self-management so important? First of all, we know from current clinical studies that a one-size-fits-all approach is inherently a hit-or-miss proposition. In any clinical study evaluating any medical protocol, there is always a group of participants who respond well and a group that either does not respond or experiences an adverse outcome. Take a look at the published data for overall drug effectiveness in managing some key chronic illnesses:
• Alzheimer’s disease: 30 percent effective
• Anti-inflammatories: 80 percent effective
• Asthma: 80 percent effective
• Cardiac disease: 60 percent effective
• Depression: 62 percent effective
• Diabetes: 57 percent effective
• Migraine: 52 percent effective
• Rheumatoid arthritis: 50 percent effective
• Cancer: 30 percent effective
Surprised? Wondering how the rate of effectiveness can be so relatively low after all the clinical trials and the years of use of these drugs? It is because we typically overlook the nonresponders in a clinical trial for regulatory approval of a drug as long as the trial is large enough that the outcomes of the responders demonstrate statistical significance against the outcomes of nonresponders. To a very great extent, therefore, when you take a medication prescribed by your doctor, you’re putting your faith in a remedy that has worked for a lot of people and has not worked for a lot of others. Cross your fingers, wear a rabbit’s foot, and pray that it works for you.
No wonder one of the pharmaceutical industry’s highest-ranking and most respected scientists, Dr. Allen Roses, onetime global vice president of genetics at GlaxoSmithKline, said back in 2003 that “most prescription medicines do not work on most people” who take them. Roses went on: “The vast majority of drugs—more than 90 percent—only work in 30 to 50 percent of the people.” It is why doctors routinely use a trial-and-error approach to drug therapy—that is, if one drug doesn’t work, try another.
The problem is compounded with polypharmacy—an individual using several drugs together in order to address the different symptoms arising from a range of causative factors. The issue here is the way the various drugs may interact with one another in the individual. There is “cross talk” among drugs; one medication may adversely influence another. An individual taking a number of different drugs simultaneously, whether he or she knows it or not, is involuntarily enrolled in an uncontrolled experiment, for it is almost certain that no study has ever been done to demonstrate the safety and effectiveness of the particular combination of medications that individual is taking. Ideally, such a review should be done—to assess not just the potential adverse reactions from combining the drugs but also the effectiveness of the combination, or its lack of effectiveness, in the individual.
I first came across the term “patient empowerment” a number of years ago, through Dr. Halsted Holman, a professor at the Stanford University School of Medicine. Holman articulated and advocated four principles of personalized and self-managed medicine that my decades of experience tell me are the right approach to both preventing and managing chronic illness. Here they are:
• There is no complete cure for chronic illness unless the cause of the individual’s own disease is discovered and successfully managed; individualized management over time is essential.
• For effective treatment of chronic illness, the individual must engage continually in different approaches to his or her health.
• The individual knows the most about his or her own condition and about the effects of certain therapies and must apply that knowledge in shaping a self-management program.
• To achieve success, the individual and the individual’s health professionals must share knowledge and divide authority.
In the next chapter, we’ll learn how the revolution in genomics is pointing the world of medicine precisely in the direction those principles embody. And we’ll see how the amazing discoveries of the genomics revolution can be harnessed to meet the global challenge we confront in the rising burden of chronic illness.