Epigenetics is a complex subject, and in reading this book you’ve grasped the main concept: that gene expression is switched on and off and up and down based on the choices you make every day and the resulting experiences that create who you are. This switching, which leads to trillions and trillions of possible combinations, is how everyday experience is transmitted to the cells of your body. But immediately a troubling problem arises. Why are some experiences so damaging to the body? Why isn’t DNA designed to preserve life as its only mission?
This is the great paradox of DNA, and it forms the next link in our story. DNA makes life possible, but at the same time it has the potential for ruinous, life-destroying actions. DNA is like a bomb that knows how to defuse itself and also how to set off an explosion. Which one will it choose? Why should the code of life be employed to create death? That’s the heart of the paradox. In all of us there are genes for developing cancer (pre-oncogenes) and opposite genes for fighting cancer (tumor-suppressing genes). This seems inexplicable until you realize that DNA reflects every aspect of existence.
Instead of choosing sides, DNA joins all sides, encompassing all possibilities. A virus or bacterium that can make you sick has its own genetic signature, which it does everything to keep intact, and so do the immune cells in your body that war against viruses and bacteria. When new cells are born, they inherit a genetic program for their death. In effect, DNA is staging a drama in which it plays the role of hero and villain, attacker and defender, keeper of life and destroyer of life.
The challenge is to make choices that activate the life-supporting side of DNA. By now you’ve seen that we’ve taken big steps in that direction. You’ve started to view life from the perspective of a cell. A cell senses its environment and makes adaptations that best serve its own survival. But it also does this using the least possible energy to maintain balance and serve its neighboring cells and the whole body. Failure to do so can lead to cancer or other diseases that can potentially kill the host and the cell along with it. So every cell naturally knows exactly what to do in all situations working in perfect harmony with its genes. Our hope is that we can do the same as human beings.
The latest research into a wide range of disorders, including heart disease, autism, schizophrenia, obesity, and Alzheimer’s, suggests that there are indicators for each disease that extend back decades in a person’s life, even to early infancy. This came as a startling discovery, because it runs contrary to our conventional notion of how we get sick. We tend to believe that getting sick follows the pattern of the common cold. You are sitting on a plane next to someone who is sneezing and coughing. Three days later you catch that person’s cold. There is a simple cause-and-effect, along with a definite starting point of infection.
Many acute illnesses do in fact follow this pattern, but it turns out that chronic disease doesn’t, and chronic disorders are the major causes of mortality in modern society. How do you organize a prevention program for a disorder decades before symptoms appear? A perplexing example of this dilemma actually showed up in the Korean War, when autopsies were performed on the bodies of young soldiers killed in battle. Males in their early twenties exhibited the fatty plaque in their coronary arteries that are the major cause of heart attacks. How did men so young have this much plaque, often enough to cause worry about an impending heart attack? There was no medical answer, and even today, the genesis of arterial plaque remains to be explained. Just as baffling, why didn’t these men suffer heart attacks at a young age, since the onset of premature heart attacks typically begins at forty? Even without satisfactory answers, here was an early clue, going back to the fifties, that chronic disease predates the arrival of symptoms by many years and has no definite beginning except at a microscopic level.
But there’s also a very hopeful side to the mystery. These early indicators hold out the best chance for preventing and curing chronic illness, because whenever the body goes out of balance, the earlier it’s caught, the easier it is to treat. Millions of people follow this principle when they take zinc tablets at the first sign of a cold or aspirin at the first hint of a headache. The same principle can be pushed back even further, which is why vaccines are effective. They give the body an advance defense against polio, measles, or this year’s flu before the disease has had a chance to develop.
In effect, a vaccine is teaching the body’s intelligence something new. The body listens (i.e., the genes respond in a new way) and learns from the new experience. “This is what measles looks like. Arm yourself.” There’s never going to be a universal vaccine for all human ills (even current vaccines have their critics and problems). Instead, we are proposing a new model for self-care; at the heart of this model is a revolutionary way of relating to your genes.
This shift in thinking agrees with every advanced trend in medicine, but the general public hasn’t absorbed as yet how radical the change will be. A new era in well-being is at hand, looking to the body’s intelligence as our most powerful ally.
To show why this approach is so urgently needed, let’s look at a dreaded disease in order to make a much bigger and more optimistic point about well-being. The disease is lung cancer. The war against lung cancer poses a stark confrontation between smoking on one hand and prevention on the other. The battle lines could hardly be clearer. Lung cancer is the leading cancer killer among both men and women, outstripping the next three cancers combined (breast, colon, and pancreatic). It surprises most people to discover that as far back as 1987, lung cancer surpassed breast cancer as the leading cause of cancer deaths among women.
The disorder would be rare if it weren’t for tobacco. In 1900, before the general spread of smoking, cases of lung cancer were so uncommon that a doctor in general practice might know of the disease only from textbooks. With the dramatic rise of smoking in modern times, tobacco-related lung cancer accounts for 90 percent of cases, and when someone stops smoking, the risks decrease year by year, although they never reach zero.
Those are the statistics (as provided by the American Lung Association), and ever since the Surgeon General forced tobacco companies to print a warning on every pack of cigarettes in 1964, sensible prevention has been clear and undeniable. (The sad fact that more women today choose to take up smoking is why lung cancer has increased among women.)
But here is where the dividing line between well-being and radical well-being shows up. The fact is, not all smokers contract lung cancer. Why not? The pathogens in tobacco smoke are almost guaranteed to damage lung tissue. A host of respiratory problems, including emphysema and asthma, loom for active smokers. Yet consider the statistics cited at http://lungcancer.about.com.
In a 2006 European study, the risk of developing lung cancer was:
0.2 percent for men who never smoked (0.4 percent for women)
5.5 percent for male former smokers (2.6 percent for women)
15.9 percent for current male smokers (9.5 percent for women)
24.4 percent for male “heavy smokers” defined as smoking more than 5 cigarettes per day (18.5 percent for women)
An earlier Canadian study quoted the lifetime risk for male smokers at 17.2 percent (11.6 percent for women) versus only 1.3 percent in male nonsmokers (1.4 percent in female nonsmokers).
These percentages translate into a story line. If you don’t smoke, lung cancer is very unlikely to strike you. If you take up smoking, the odds against you increase in a straight line. However, even if you fall into the highest risk category of “heavy smokers,” 75 percent of the time you won’t contract lung cancer.
We aren’t remotely suggesting that you take your chances and start smoking. The story line actually leads in a very different, and unexpected, direction. Why do some smokers dodge the bullet? This is the million-dollar question that statistics do not readily address. What you and I and every other individual want to know is how our situation will turn out. Lung cancer is only one horrible example. The statistics around every disease point to some people who manage to escape getting ill. “How do I become one of those people?” is the question that naturally arises.
The answer is genetic, but it goes far beyond the cliché that some people have good genes and some people have bad genes. Imagine tobacco smoke entering the lungs of two people. The toxic chemicals in the smoke are the same for both; the known carcinogens are the same. When the smoke hits the outer lining of lung tissue, damage is bound to occur—but not necessarily in the same way or to the same degree.
Cells are very resilient, and they make choices all the time. Over millions of years of evolution, one choice stands out. Cells choose to fight back against any threat to their survival. A major threat, and the one that applies to tobacco smoke, is deleterious variants that arise in genes called pathogenic mutations. The toxins in tobacco smoke can cause a sudden mutation that leads to a distortion in how the cell operates. But DNA knows how to regulate and repair itself, and the norm is for damaging mutations to be destroyed. There’s a limit to a cell’s healing abilities, but the cell isn’t simply poisoned to death. With enough exposure to the toxins in tobacco, some distortions will inevitably get by the cell’s defenses, and if enough damage occurs, and if the damage is of a precise kind, disaster follows. The cell forgets how to divide normally. A cell that goes on the path of rampant division, overwhelming adjacent cells in its unregulated growth, has become cancerous.
You can see where the story line has now taken us. Behind the statistics for the whole population, the beginning of a malignancy is about single cells deciding what to do, guided by their DNA. Let’s press the investigation further. When three out of four heavy smokers escape lung cancer (by no means are they guaranteed to escape other serious illness), what choices did their cells make? For it’s those choices that actually rescued them.
The best medical knowledge has this to say: Some people are better at fending off toxins than others. Some DNA is better at repairing itself and destroying harmful mutations. Many factors are at work in how a cell heals, and its escape from danger is blurred into everything else that’s happening to it. When it comes to a cell and how it escapes disease, there’s a lot of room for uncertainty. Knowing how a typical cell makes decisions doesn’t tell us how your cells make decisions. Everyone’s cells are different, based on their specific component of genes and the gene activities you impart to them with your lifestyle. There’s also the whole issue of the paths your cells will make a day, a month, or ten years from now, because like people, cells can be fickle and changeable, depending in part on the choices you make.
We’ve been dwelling on a grim subject in order to shed light on something positive, the enormous intelligence and resilience of the cell, meaning your cells. Research has shown that thousands of potentially damaging abnormalities are detected and destroyed in our bodies every day. What makes the difference between well-being and radical well-being is learning to guide and influence your genes in a positive manner.
We said that you are more than your genes, just as you are more than your brain. You are the user of your genes and your brain. The key is learning how to use them so that they afford you optimal health and happiness. Everything you want to be, every achievement you want to reach, every value you want to uphold must pass through your brain and your genes in order to become real. So learning to communicate with your genes isn’t just a nice add-on. It’s essential. You are already communicating with your genes, but most of the messages you’re sending to them are unconscious. Repetition plays a large part. Reactions become automatic and ingrained. This is a terrible waste of your potential to make free choices.
Genetics would be much simpler if it traveled down a one-way street where gene A could always be connected to disorder B. Linear cause-and-effect is simple and satisfying. But genes operate on a two-way street, with messages constantly traveling back and forth—or, to be more accurate, the road is a six-lane superhighway, loaded with messages coming from all directions.
This realization is having a huge ripple effect throughout medicine and biology, overturning what we thought we knew about the brain, the life of a cell, and almost every form of disease. To give a prime example, we’ll look at the present situation in depression, which directly or indirectly has touched almost everyone’s life, either through their own suffering or that of a family member or friend.
About 20 percent of people will experience a severe depression sometime in their lives. At the moment, there is a rash of depression among combat soldiers who served in Afghanistan (directly related to a sharp increase in suicides among Afghanistan war veterans, suicide being generally linked to depression) and among laid-off workers who are enduring long-term unemployment. In both cases, an outside event led to the depression, but we do not know why, in the sense that only a certain percentage of people become depressed under the same stimulus (war and losing a job).
The link between depression and genes has proved elusive. Nothing as simple as a “depression gene” exists. Early in 2013, the magazine Science News began an article on depression with a blanket judgment: “A massive effort to uncover the genes involved in depression has largely failed.” This news sent shock waves through the medical community, but its impact hasn’t really hit the public, which keeps funding the multibillion-dollar drug industry and its constant production of new—and supposedly better—antidepressants. Twenty-seven years after Prozac came on the market in 1988, around one in five Americans takes a psychotropic (mind-altering) drug, despite the proven risk of side effects. Prozac, for example, has three common side effects (hives or skin rash, restlessness, and the inability to sit still); two less common ones (chills or fever and joint or muscle pain); and twenty-five rare ones (including anxiety, fatigue, and increased thirst), according to the website www.drugs.com.
The connection to genes isn’t brought up when the physician is prescribing a drug to relieve a patient’s suffering. However, genes are the pivot between a drug that works and one that doesn’t. The model for depression that has been accepted for decades labels depression as a brain disorder. Yet brain disorders are rooted in genetics. The logic is deceptively simple. If you feel depressed, there is an imbalance in the brain chemicals responsible for moods (chiefly the neurotransmitters serotonin and dopamine). Thus in depression, the cellular mechanism that produces these chemicals must be impaired, which comes down to impaired genes, since genes are the starting point for every process taking place inside a cell.
Why didn’t this simple logic turn out to be true? As prominent researchers now concede, the genes of depressed people are not damaged or distorted compared with the genes of people who aren’t depressed. What follows from this finding is that other basic assumptions are wrong. The most popular antidepressants supposedly worked by repairing chemical imbalances in the synapses—the gaps between two nerve endings—where the culprit was an imbalance of serotonin. But serotonin is directly regulated by genes, and some key research indicates that either drugs aimed at fixing the serotonin problem don’t work that way or there wasn’t a serotonin problem in the first place. The Science News report didn’t leave much wiggle room on this point: “By combing through the DNA of 34,549 volunteers, an international team of 86 scientists hoped to uncover genetic influences that affect a person’s vulnerability to depression. But the analysis turned up nothing.” (The study being referenced was published in the January 3, 2013, issue of Biological Psychiatry.)
Nothing doesn’t mean something. If the chain of explanation running from genes to the synapses and finally to the pharmaceutical lab is broken, a host of doubts arises. Is depression a brain disease in the first place, or is it, as psychiatry assumed before the arrival of modern drug treatment, a disorder of the mind? The latest theories haven’t gone back to square one. What we know isn’t black and white. There are multiple variables in depression, which leads to some fairly good conclusions:
There are many kinds of depression. It isn’t a single disorder.
Each depressed person displays their own mixture of possible causes for their symptoms.
The mental component in depression includes upbringing, learned behavior, core beliefs, and judgment about the self.
The brain component includes wired-in neural pathways, with suggested weaknesses in certain areas of the brain whose cause isn’t understood.
Depression can’t be isolated to one region of the brain. The interaction of multiple regions is involved.
As you can see, these conclusions scuttle a simple cause-and-effect model. “If you have a headache, take an aspirin” doesn’t translate into “If you feel depressed, take an antidepressant.” The susceptibility to depression is as complex as gene expression itself. Why does depression run in families, as it’s known to do? Again, there’s no simple answer. No gene or group of genes that you inherited seems to guarantee that you will become depressed. We are talking instead about genes that make you susceptible to the disorder. What triggers these (unknown) genes remains a mystery. The same genetic predisposition could be hidden in one child who never becomes depressed when he grows up and in another child who somehow gets triggered into depression. Do social interactions, for example, make someone feel helpless and hopeless? That’s how depression feels, so perhaps (in the epigenome) enough bad memories of feeling left out or ostracized from others lead to a tipping point and depression emerges.
In our opinion, depression isn’t a brain disorder looking for a magic bullet to solve it, and the whole disease model must be drastically changed. Even as a medical diagnosis, it’s suspect. The big study about the failure to find the genes responsible for depression ignored diagnoses of depression and went with symptoms instead. Asking people about their symptoms resulted in a lower number of those who would be considered depressed. Perhaps some people are in denial or don’t know the difference between depression and ordinary sadness. But more important, symptoms change over a lifetime, and there is a sliding scale for each sufferer. Like emotion in general, depression comes and goes. It feels different one day than it does another.
So will depression ever be curable? The situation is too cloudy for anyone to offer either a pessimistic or optimistic prediction. Drug treatment remains hugely popular, no matter what the basic science says. In cases of mild to moderate depression—the most common type—antidepressants sometimes don’t work better than 30 percent of the time, around the same as the placebo effect. Some symptoms of severe depression remain intractable, and yet in other cases, the chronically depressed perform the best with drug treatment. Hope is always better than giving up.
Now that you understand the situation, with all its uncertainties, you are ahead of the curve, because the vast majority of doctors turn their back on the research and keep prescribing the same antidepressants. Millions of patients continue to take them, feeling that there is no other way. But there is. Depression doesn’t fit the old disease model, but it does fit the new model we’ve been describing. Depression involves lifestyle and environment. Genes play a part but so do behavior, beliefs, and how a person reacts to everyday experiences. The epigenome is storing genetic reactions of personal experiences and memories, leading to the constantly shifting activities of your genes.