I’m one of those people you hate because of genetics. It’s the truth.
—Brad Pitt
You inherit your environment just as much as your genes.
—Johnny Rich, American author and entrepreneur
In 2012, the actress Angelina Jolie was found to have a faulty copy of a gene called BRCA1 that her doctors claimed gave her an 87 percent chance of getting breast cancer. To prevent this, she had her breasts removed and replaced. This was supposed to reduce her risk of getting breast cancer to less than 5 percent. She encouraged others to consider doing the same when she said, “I want to encourage every woman, especially if you have a family history of breast or ovarian cancer, to seek out the information and medical experts who can help you through this aspect of your life, and to make your own informed choices.” Jolie’s mother and grandmother had cancer, giving her added motivation to take action.
The question I am going to investigate in this chapter is whether her doctors were correct to say that having the BRCA1 gene gave her an 87 percent chance of getting breast cancer. It is an important question for this book, because if our health is mostly determined by our genes, what is the point of trying to do anything about it? This is related to the age-old debate about whether our genes or our upbringing and environment are more important in shaping our traits and prospects—often called nature versus nurture. Whereas advances in genetics during the second half of the twentieth century seemed to support the power of nature, more recent discoveries in the field of epigenetics have seen the pendulum swing, giving nurture—the environment—an equally prominent role. We will see that our environment shapes us as much as our genes, and our environment can actually affect our genetic makeup. More than that, since the cell’s environment is affected by emotions and thoughts, positive thinking and relaxation can also affect our genes.
While even the earliest of cavemen and cavewomen presumably noticed the physical similarities between children and their parents, humans only began to understand why that is the case around 150 years ago. Our bodies are made up of cells. The middle of these cells has a kind of control center called a nucleus. Within the nucleus are things called chromosomes. The best-known chromosomes are the sex chromosomes. Females have two X chromosomes, and males have one X and one Y chromosome. There are in-between cases, too, but that covers the basics. We normally get twenty-three chromosomes from our mother’s egg and twenty-three from our father’s sperm, and that is supposed to determine what kind of person you are.
Looking even more closely, we see that chromosomes are made up of large deoxyribonucleic acid (DNA) molecules. The DNA molecules contain instructions for how to build, develop, and reproduce all living things and some viruses. A gene is simply a section of DNA. The genes are sections that are responsible for specific parts of the body, such as eye color, number of limbs, and blood type.
The reason some believe we are largely the product of our DNA is that it carries instructions about how to make proteins. Proteins, in turn, are the building blocks of our bodies, like the bricks of a house. To name a few examples, antibodies are proteins that help protect the body against viruses; enzymes are proteins that carry out all of the chemical reactions that take place inside cells; growth hormones are proteins that help cells grow and reproduce; actin is a protein that helps muscles contract; and ferritin is a protein that stores iron and releases it in a controlled fashion.
Since humans are basically bundles of proteins built according to instructions contained in our DNA, it is no surprise that some scientists came to believe that the key to understanding our species could be found there. Accordingly, scientists set out to learn more about DNA and genes.
They found genes that determine eye color, skin color, and height, although of course humans already knew these traits could be inherited. They also found genes that increased the risk of some diseases like hemophilia, cystic fibrosis, and Huntington’s disease. The hope was that the discovery of these genes would lead to the development of genetic cures for the diseases to which they were linked.
Genes were also found that seemed to influence our mind. Some studies identified gene mutations associated with autism, attention deficit hyperactivity disorder, depression, bipolar disorder, and schizophrenia. It should be noted this research did not show these genetic variants caused these conditions, only that they were associated with them. There is even an ongoing search for genes linked to happiness. All these discoveries about genes made many scientists believe that once they learned everything about genes, they would know everything about us. Forget all this positive-thinking mumbo-jumbo, they thought, let’s look at genes. This line of thinking led to the launch of the Human Genome Project.
In 1990 the US government invested $3.8 billion in the Human Genome Project. It led to some successes, including improved diagnosis of some cancers and personalized blood-thinning medication. Couples using in vitro fertilization can screen their embryos for hereditary diseases. Yet the Human Genome Project and genetic medicine more broadly have not come close to revolutionizing health the way that antibiotics, anesthesia, or polio vaccines did, and it has been much more costly.
The growing personalized-medicine movement, which attempts to discover targeted drugs for people with certain genetic profiles, has so far failed to deliver on even a fraction of the promises made for it. Cases like that of Angelina Jolie’s faulty BRCA1 gene might make the headlines, but they do not really add much to what we already knew. Doctors could have told Jolie that she had a high risk of cancer, based on her family history, before the invention of the BRCA1 test. In the end, many people admit that the Human Genome Project has been an expensive flop.
In 2010, New York Times writer Nicholas Wade reported:
Ten years after President Bill Clinton announced that the first draft of the human genome was complete, medicine has yet to see any large part of the promised benefits.
Worse, the Human Genome Project revealed or confirmed several facts that undermine the very role of genes in determining what our body, mind, and health are like.
For one, all the cells in your body, whether they are part of your hair, heart, or skin, have pretty much the same DNA. Yet the cells themselves are not the same: a bone cell is very different from an eyeball cell. The DNA of bees is even more strange. Queen bees and worker bees are distinct, with the queen being large and laying eggs and the workers being small and infertile, but they have the same DNA. Even more puzzling is that red blood cells don’t even have a nucleus or DNA, yet they still live. If DNA is the source of our biology, how can cells and bees with the same DNA be so different?
Furthermore, scientists were surprised to learn that mice have roughly as many genes as humans do (about 20,500). Even very simple species such as fruit flies and worms have about half as many genes as humans. We are more than twice as complex as worms, so why do we have only twice as many genes? Even weirder is that scientists don’t know what most genes do, with 98 percent of our DNA being classified as junk DNA. If genes are so important, why are most of them junk? Stranger still, you can remove a cell’s nucleus, which contains its DNA, and the cell can live for several months without changing its behavior. If DNA is the genetic blueprint that controls everything about the cell’s function, how can cells survive without it?
You don’t need to be a geneticist to know that a baby boy born with a gene associated with being tall will not grow up to be tall if nobody feeds him properly. And if a girl is born with a gene associated with intelligence, assuming for a moment that such a thing exists, she will not reach her intellectual potential if she is not stimulated. We all know that the environment, or nurture, plays a strong role in the development of humans and other species. The hype surrounding the Human Genome Project led to exaggerated beliefs about the importance of genes.
At the other end of the spectrum from the belief that our genes are responsible for everything is the tabula rasa, or blank slate, theory. According to this view, our environment is the only important thing and genes play no role at all.
Most contemporary psychologists believe that personalities can be modified. This should not be surprising, since if we could not modify our personalities, psychology as a profession would not exist. The American psychologist John Watson famously said if he had control of the environment a child grew up in, he could turn the infant into a doctor, a lawyer, a thief, or a painter. Watson and fellow psychologist Burrhus Frederic Skinner believed the mind was a blank slate, or tabula rasa, at birth, after which we develop our traits as a result of our environment and our behavior. They attribute everything about our personalities to nurture and none whatsoever to nature.
The 1983 comedy film Trading Places plays on this theory. Eddie Murphy starts off as a beggar, while Dan Aykroyd is the top manager in a successful private business run by two elderly brothers. The brothers bet that they can turn Murphy into a successful manager and Aykroyd into a beggar if they change their circumstances. They take everything away from Aykroyd and give everything to Murphy and watch what happens. I won’t give away the ending for those of you who haven’t seen it—if not, I recommend you do purely for a good laugh.
If the tabula rasa theory is true, then genes play no role in our personalities. But just as exaggerating the role of genes is a mistake, so is downplaying the role of what we are born with. Our environment can influence us, but any parent or obstetrician will tell you that children are also born with their own personality traits. The first thing the doctor said about my sister Samantha was that she had a good set of lungs, because she cried very loudly. She doesn’t scream or cry anymore, yet I am sure she would be happy to acknowledge that she is still very expressive.
The same thing applies to health. Someone predisposed to cancer who decides to smoke is more likely to get cancer than someone similarly predisposed who does not smoke. In fact, common sense dictates that both nature (our genes) and nurture (our environment) play roles in both our health and our personalities. The emerging science of epigenetics even shows that the environment can influence our genes.
Jean-Baptiste Lamarck, an eighteenth-century French soldier turned biologist, believed that the environment could change a species and what they passed on to their offspring. To Lamarck, a giraffe might develop a slightly longer neck after a lifetime of striving to reach higher and get the tasty leaves that other giraffes could not reach. Its babies would then inherit its longer neck. This ran against standard evolutionary theory, according to which a giraffe might develop a longer neck through a random genetic mutation. Then, because the giraffe with the genes for the longer neck was able to reach more leaves, it would be less likely to starve and more likely to have offspring. In this way, the accidental beneficial gene would be favored and passed on. The outcome in Lamarck’s theory and the other standard theories is still the same: Giraffes get longer necks.
However, whether humans change through random gene mutations or conscious intention has profound implications for how we approach our body, our relationships, and life in general. If it is all decided by our father’s sperm, our mother’s egg, and random genetic mutations, what is the point of striving for the human equivalent of that higher leaf? And what is the point of investing in social programs that can help? On the other hand, if our efforts can affect our biology and even our offspring, maybe it is worth it.
For a while, science seemed to be against Lamarck because of an experiment with mice. In 1889, German evolutionary biologist August Weismann cut off the tails of mice for twenty-two generations and did not find that the mice tails became shorter over the generations. Against this background, American science writer Martin Gardner declared Lamarckism to be officially dead in 1957.
In fact, Gardner was wrong. Lamarck’s theory was partly right, whereas Weismann’s experiment was faulty. When scientists removed the mice’s tails, it was not the same as when giraffes were trying to reach higher to get more leaves. Lamarck was clear that the trait passed on to further generations if it involved a willful overcoming of obstacles. A number of studies that I will discuss below show that Lamarck was partly correct, and why this is important for our health.
The more mother rats lick their pups, the less stress they have. More than that, the genes responsible for releasing stress hormones become suppressed, and this can be passed on to the next generation. Similar things can happen with humans. The rural Swedish district of Överkalix has had many famines over the last 150 years. Men whose grandfathers had endured a failed crop season, and had therefore survived starvation conditions before puberty, lived longer than men whose grandfathers had not experienced a failed crop season. In a similar study, researchers in Bristol found that men who smoked before puberty had fatter sons than those who did not. In both of these cases, changes caused by a person’s environment were being passed on to offspring later down the line.
If genes determine our biology, there is not much we can do to affect genetic diseases (and according to genetic extremists, diseases must be genetic by definition) other than changing our genes, perhaps by doing lots of expensive research on even more expensive genetic medicine. On the other hand, if we can influence our genes, then things are, at least partly, in our hands. Professor Dean Ornish at the University of California, San Francisco, did a trial showing the important health implications of epigenetics.
Ornish’s trial involved thirty men who had a small risk of getting prostate cancer. They agreed to do yoga and exercise, switch to a low-fat diet rich in vegetables and fruits, and take vitamin C supplements. They also agreed to go on a three-day intensive retreat. In the retreat, Ornish surrounded the men with furniture, music, and reading material from the time of their youth to create the same atmosphere that would have existed when they were younger. He was trying to make the men feel younger. When they were tested three months after the beginning of the study, the men had lower stress levels and lower cholesterol. Most significantly and surprising of all, their genes associated with the prostate cancer had changed and now indicated a lower risk. Other trials are beginning to confirm that lifestyle interventions, such as the one Ornish designed, can influence our genes.
The easiest way to understand epigenetics is to think of DNA as an architectural blueprint for creating proteins. The proteins, in turn, make up your body. Eric Lander of the Massachusetts Institute of Technology was one of the scientists who led the Human Genome Project. He explains epigenetics by analogy with a Boeing 777 aircraft. The DNA is like the parts list of the plane. You still need some instructions for how to put the parts together. The environment around the cell provides these instructions, and the instructions can be passed from generation to generation.
Even more recent than epigenetics, however, is the growing excitement in the last three to four years around precision genome editing. Might this push the pendulum in the nature/nurture debate back in the direction of nature?
Scientists in the late 1980s and early 1990s noticed something odd about the DNA of bacteria. They spotted strange repetitive sections of DNA they called clustered regularly interspaced short palindromic repeats (CRISPRs). They found them to be part of a pretty cool immune defense mechanism. Bacteria store samples of invading viruses’ DNA within their own DNA between CRISPRs, thus creating a kind of enemy mugshot reference library that they can use to recognize and attack previously encountered viruses. Some of the key work to reveal this was published in 2007 by scientists at the Danish food company Danisco, which used the discovery to produce yogurts and cheese that were less susceptible to viral attack.
Other scientists were quick to spot the wider potential. In 2012–13, other researchers demonstrated that the CRISPR mechanism could be used to turn off unwanted genes, or even to insert a new gene into a cell’s DNA. The technique is cheaper, quicker, and easier than previous genome-editing techniques, and thousands of scientists have adopted it. CRISPR has been hailed by some as among the most significant advances of the last fifty years for its ability to help scientists to target, study, and therefore understand what specific parts of our DNA actually do. They also think that CRISPR might help treat or even eradicate diseases that result from genetic errors.
Whether CRISPR lives up to this potential remains to be seen. If it does and we are able to develop ways to treat or wipe out diseases caused by genetic variants, might this show the previous optimism around genetics was justified after all? Were those who emphasized the role of nature over nurture right in the end?
In a word, no. There are some diseases that are caused by defects in single genes, as we have seen, such as cystic fibrosis and Huntington’s disease. The use of CRISPR to treat these and other conditions caused by single genes would be major medical breakthroughs. However, in most cases, illnesses are only partially heritable, and often environmental and lifestyle factors are more important than genes. There is evidence that our thoughts and our mind might also be able to affect our genes.
If our genes cause happiness, sadness, and depression, there is nothing we can do other than pray for the development of a therapy to fix our (un)happy genes. Epigenetics calls this into question, because it shows that even if there were a happy gene, we can probably influence it, not only for us, but for our children, too. But how can we influence our genes? Many things in our environment determine which genes get expressed. They include the food you eat, the quality of the air you breathe, and whether you smoke.
Beyond bad air and food, our cells also respond to our emotional environment. Your blood is basically the immediate environment of all the cells in your body. Under stress, the body releases cortisol and adrenaline into the bloodstream. And remember that your mind is partly in control of whether you activate your stress response. Here is the cool thing: Since your mind influences whether you induce the stress response, and the stress response changes the environment of your cells, and the environment of your cells determines whether certain genes are expressed, it follows that your mind can influence your genes.
Too much stress (often caused by not taking the time to relax) activates the sympathetic nervous system, causing higher levels of cortisol and adrenaline in your blood. This doesn’t just affect how you feel, it affects your DNA, too. A recent systematic review including forty-three studies found that higher levels of stress hormones like cortisol can damage your DNA by increasing the chances of unwanted gene mutations. The stress response also affects how the cells produce proteins that your body needs to grow, repair, and defend itself from diseases, including cancer. All these harmful effects are counteracted when you take the time to induce the relaxation response. When you act and react in a relaxed, loving way, cortisol and adrenaline levels don’t rise to damage your DNA and your body. And, as epigenetics suggests, your offspring will be less likely to experience the negative effects of stress.
The idea that our DNA determines the shape and health of our bodies, and even our personalities, left everything from our eye color and height to our mental disposition up to nature, our father’s sperm and our mother’s egg. As we have just seen, the excitement surrounding the Human Genome Project reinforced the importance of genes and generated many exaggerated claims about the power of genes and therefore of genetic medicine. In a way, the science of epigenetics takes us back to common sense. Genes are important, but so is the environment. The thing epigenetics adds is that the environment does not affect us independently of our genes: our environment affects the very genes we pass on to our children as well. While the field is relatively new and the extent of the influence of our environment on our genes is not fully known, it clearly shows that genes are not as important as some previously suggested.
As for Angelina Jolie, her family background made her desire to protect herself from getting breast cancer understandable and right. On top of that, cancer is a terrible, scary disease and the way people deal with it is personal. We need to respect that, and I admire Jolie’s courage in making her difficult decision public.
The question here is whether having a faulty version of the BRCA1 gene gave her an 87 percent chance of developing breast cancer, as her doctors led her and then us to believe. Although I don’t have access to Jolie’s test results, the best evidence suggests that in most cases the chance would be closer to 57 percent. And while there are some exceptions, including the BRCA1 gene, cancer in general may be only 10 percent connected to genes.
We’re going to keep reading about new genetic discoveries and medicines that promise to unlock some secret of our biology or cure some disease. How good are these promises likely to be? In a word: not very. In most cases, illnesses are only partially heritable, and often environmental and lifestyle factors are more important than genes.
A summary of studies on twins published in 2010 by Cecile Janssens of Emory University estimated the genetic proportion of many diseases. Twin studies are great because identical twins have the same genes, so if they have different diseases, then diseases must be caused by some environmental (nongenetic) factor. In the study, Janssens found that the genetic component of diseases is highly variable.
Here are a few examples of diseases and the percentage caused by genetic factors: type 2 diabetes (26 percent); breast cancer (27 percent); anxiety disorder (32 percent); depression (37 percent); prostate cancer (42 percent); heart attack (38 percent for men, 57 percent for women); migraine (45 percent); rheumatoid arthritis (53 to 65 percent); obesity (75 percent for men, 77 percent for women); Alzheimer’s disease (79 percent); schizophrenia (81 percent); and type 1 diabetes (88 percent).
Therefore, in most instances, factors like diet, exercise, air quality, stress level, and social relationships will remain important for our health and life chances no matter how far new technologies push forward the boundaries of what we know about the roles and significance of specific parts of our DNA.
Unfortunately, the exaggerated attention given to genetic factors in disease by the media means that environmental causes and preventative measures are often ignored or downplayed. It is important to note that many of these claims are exaggerated to understand this book. If our genes determine our health, there is not much point in trying to think healthier thoughts or adopt better habits. On the other hand, if we know that the environment is equally important (which it is), this can motivate us to make positive changes.
The lifestyle interventions such as the ones in Dean Ornish’s study don’t only work by affecting your body and mind at the level you can see: They also affect your underlying DNA. Dean Ornish’s interventions involved:
Doing all of these things may be difficult at first; however, choosing one of them is not. Adding a large, healthy salad to your meals and eating more fruit takes only a tiny bit of planning. For some of us, doing exercise comes quite naturally. If it doesn’t, join an exercise group with people you like. As for putting yourself in a place that reminds you of your youth, that is very easy. Simply do something (safe and healthy) that you used to do when you were a teenager.