Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives

by Michael Specter

  That depends on what you learn. If, for example, you discover that you possess a greatly increased risk of developing type 2 diabetes or heart disease, there are changes in diet and lifestyle that can help. There are also numerous medications. Will they help enough? Nobody will know until more genetic information is available. The tests have already proven their value in other ways, though. Genome-wide association tests have revealed how abnormal control of inflammation lies behind one of the principal causes of age-related macular degeneration, which is a leading cause of vision loss in Americans sixty years of age and older. More than one promising drug is already under development. The tests have also discovered genes that reveal pathways of inflammation critical for the development of inflammatory bowel disease, as well as genetic pathways for heart disease, diabetes, and obesity.

  A principal goal of this research is to provide doctors with information that will take the guesswork out of writing prescriptions. In the case of the blood thinner warfarin that has already begun to happen. Warfarin is prescribed to two million people each year in the United States. The proper dose can be difficult to determine, and until recently doctors simply had to make an educated guess. Too much of the drug will put a patient at high risk for bleeding; too little can cause blood clots that lead to heart attacks. The dose can depend on age, gender, weight, and medical history. But it also depends on genetics. Two versions of the CYP2C9 gene can retard the body’s ability to break down warfarin. This causes the drug’s concentration in the bloodstream to decrease more slowly, which means the patient would need a lower dose. Armed with that kind of information—which these tests now provide—a physician is far more likely to get the dose right the first time.

  That is the essence of pharmacogenetics. If three people out of a thousand die during a clinical trial due to a drug reaction, that drug will never make it to the market in the United States, even though it would have worked without complications for more than 99 percent of patients. If we knew who those three people were likely to be, however, none of that would matter. Obviously, that kind of knowledge would have saved thousands of lives lost to Vioxx. And it would have permitted millions who were not at risk of heart attack or stroke to continue to take a drug that had helped them immensely.

  “We are just starting all this,” George Church said. In addition to his academic and entrepreneurial commitments, Church advises several genomics companies, including 23andme. “But there is already great value to these tests. If you happen to have a SNP that leads to a disease that changing behavior will help, then it’s magnificent. So if you have a propensity to diabetes, you’re going to want to exercise, don’t eat certain things, etcetera. If you have a propensity to a certain type of heart disease, etcetera, etcetera. If you have a propensity towards Alzheimer’s, you might want to start on a statin early, you know?”

  AFTER WALKING OUT of Church’s laboratory at Harvard, I took a cab to the airport and flew home. It wasn’t a pleasant flight because I couldn’t stop thinking about the terrifying phrase “propensity toward Alzheimer’s.” Who wouldn’t fear a disease that starts by making us forget much of what we would choose to remember and ends in feral despair? I have special reason to worry. A few years ago my father began to disappear into a cloud of dementia. His illness took the normal pattern—first forgetting keys (as we all do), then names, then simple directions, and eventually whatever you had told him five minutes before. Inevitably, he became incapable of fending for himself. I can think of no worse fate.

  For most common diseases, the relative risks posed to individuals by specific genetic mutations remain unclear. There are just too many moving parts we have yet to analyze. Alzheimer’s is an exception. Genomic studies have provided compelling evidence that a variant of at least one protein, called APOE and found on chromosome 19, dramatically increases the risk of developing the disease. APOE contains the instructions necessary to make a protein called apolipoprotein, which plays a complicated role in moderating cholesterol and clearing fats from the blood. There are three common forms, or alleles—APOE2, 3, and 4. APOE4 is the time bomb.

  People with two copies of APOE4 have fifteen times the risk of developing Alzheimer’s than a typical person of similar ethnic heritage. They are also at great risk of losing their memory far more rapidly than people without this allele, or those who have just one copy. The correlation between APOE4 and Alzheimer’s disease is so dramatic that when James Watson became the second person (Craig Venter was the first) to publish his entire genomic sequence in 2007, he chose, of all the billions of nucleotides that comprise his DNA, to block only that data. There is Alzheimer’s in Watson’s family, and despite his age—he was seventy-nine at the time—Watson said he didn’t wish to know the status of such a debilitating disease for which there is no cure.

  Many, perhaps most, people would make the same decision, choosing to subscribe to that well-worn aphorism from Ecclesias tes: “With much wisdom comes much sorrow; the more knowledge the more grief.” Others adhere to a more radical, denialist vision: “Ignorance is bliss.” I prefer to see fate the way Lawrence of Arabia saw it after he managed to cross the Nefud desert. “Remember,” he said to a stunned Ali, who had warned that the trip would kill Lawrence, the camels, and all his men. “Nothing is written unless you write it.” It’s not as if I believed that knowledge would permit me to alter my prospects of developing Alzheimer’s, but it would surely permit me to alter everything else in my life.

  “There’s almost nothing that you can’t act on in some way or another,” Church had told me at Harvard. “It’s probabilistic just like every decision you make in your life. What car you’ve got, whether to jog or not. You can always—if there’s no cure, you can make a cure. You can be Augusto Odone. You can do the next Lorenzo’s Oil. You may not be successful, but at least it will keep you busy while you’re dying, or somebody in your family is dying.

  “And I would definitely prefer to be busy than to be ignorant,” he continued. “In other words, ‘Gee, I don’t know if I have the Huntington’s gene, so I don’t know if I should go out and raise money and get educated.’ I think an increasing number of people are going to be altruistic—or selfish, depending upon how you look at it—and say, ‘I want to know, so I can spend a maximum amount of time with my loved ones, fixing the family disease.’”

  I had already signed up for the tests offered by Navigenics, deCODE, and 23andme. My APOE status was included on my Navigenics report, and it never occurred to me not to look.

  A few days later, I poured myself a cup of coffee, sat down, and signed in to the Web site, where my data was waiting. Like the other companies, Navigenics issues a detailed guide, which it calls your Health Compass, that assesses the risks associated with many of the SNPs in your profile. (At the time it was the only company to provide customers with their APOE status, although at first it had done so by a complicated and misleading route that involved testing a different gene, one that is often inherited with APOE.)

  I downloaded the 40,000-word report on my personal health. Each condition was described in three ways: as a percentile, which showed where my risks ranked compared to the sample population; as the likelihood that I would develop a given condition over my lifetime; and compared to the average person’s risk. I held my breath and turned to page six, where I discovered that my lifetime risk of developing Alzheimer’s—4.4 percent—was half that of the average man with my ethnic background. I don’t have either APOE4 allele, which is a great relief. “You dodged a bullet,” my extremely wise physician said when I told him the news. “But don’t forget they might be coming out of a machine gun.”

  He was absolutely right. As is the case with heart disease, diabetes, autism, and many other conditions, there will almost certainly prove to be many causes of Alzheimer’s. One theory holds, for example, that in some cases cholesterol may play a significant role; people with Alzheimer’s often accumulate too much of a substance called amyloid precursor protein (APP). We all produce AP
P, but in people with Alzheimer’s disease the protein gives rise to a toxic substance called beta amyloid that builds up and eventually causes plaques that kill brain cells. There remains much to be learned about this process, but some doctors recommend that people with a family history of Alzheimer’s disease take statins, which help to reduce cholesterol levels even when the results from standard cholesterol tests are normal.

  This is when I realized that becoming an early adopter of personal genomics isn’t like buying one of the first iPods or some other cool technological gadget; there is a lot more at stake. My tests showed that I have a significantly increased risk of heart attack, diabetes, and atrial fibrillation. These are not solely diseases influenced by genetics, and effective measures exist to address at least some of those risks—diet and exercise, for instance. That’s the good news. Adding that data to my family history of Alzheimer’s disease suggests that it would probably make sense for me to begin taking a statin drug to lower cholesterol (even though mine is not high).

  But complex as those variables are, it’s still not that simple. About one person in ten thousand who take statins experiences a condition known as myopathy—muscle pain and weakness. (And since millions of Americans take the drug, those numbers are not as insignificant as they might seem.) It turns out that I have one C allele at SNP rs414056, which is located in the SLCO1B1 gene. That means I have nearly five times the chance of an adverse reaction to statins as people who have no Cs on that gene. (It could be worse; two Cs and your odds climb to seventeen times the average.) Now, what does that mean exactly? Well, if the study is correct I still have far less than a 1 percent chance of experiencing myopathy. I’ll take those odds. As 23andme points out in its description of the statin response, “Please note that myopathy is a very rare side effect of statins even among those with genotypes that increase their odds of experiencing it.” The risks of heart disease, however, and, in my family, Alzheimer’s disease, are not rare.

  CRUISING THROUGH ONE’S genomic data is not for the faint of heart. Thanks to 23andme, I now know that I am left-eyed and can taste bitter food. Cool. But I am also a slow caffeine metabolizer. That’s a shame, because for people like me coffee increases the risk of heart attack, and I already have plenty of those risks. The information, though, helps explain a mystery of my youth. I drank a lot of coffee, and periodically I would see studies that suggested coffee increased the risk of heart disease. Then other reports would quickly contradict them. With this new genetic information those differences start to make sense; some people react badly to a lot of coffee and others do not. I ended up with genetic bad luck on the caffeine front and have no choice but to drink less of it.

  I’m not resistant to HIV or malaria but I am resistant, unusually enough, to the norovirus (which is the most common cause of what people think is stomach flu; actually, it’s not flu at all). My maternal ancestors came from somewhere in the Urals—but I also have a bit of Berber in me because at some point seventeen thousand years ago, after the last Ice Age, my paternal line seems to have made its way into northern Africa.

  If the calculations provided by these tests fail to satiate your curiosity, you can always analyze the million lines of raw data that spell your DNA (or at least as much of it as these companies currently process). You can download the data in a Zip file as if it were a song from iTunes or some family photos. Then simply plug that information into a free program called Promethease that annotates thousands of genotypes and spits back unimaginably detailed information about whatever is known about every SNP. Promethease is not for everyone, or really for very many people. It’s so comprehensive that it is difficult to interpret—sort of like getting all the hits from a Google search dumped in your lap (and for most people, in a language they don’t speak).

  These are still early days in genomics, but it won’t be long until people will carry their entire genome on their cell phone—along with an application that helps make sense of it all. When you pick up those dozen eggs at the store your phone will remind you that not only do you have high cholesterol but you have already bought eggs this week. It will warn a diabetic against a food with sugar, and a vegan to skip the soup because it was made from meat stock. It would ensure that nobody with hemochromatosis slipped up and bought spinach, and in my case, when I buy coffee beans, it would nag me to remember that they had better be decaf.

  Someday—and not so long from now—medicine really will be personal. Then everyone will be a member of his own race. When that happens one has to wonder, Will discrimination finally disappear, or will it just find a new voice? That’s up to us. In literature, scientific future is often heartless and grim. The 1997 film Gattaca was a work of science fiction about a man burdened with DNA he inherited from his parents, rather than having had it selected for him before conception. Most people were made to order. But not the main character, Vincent. He was a member of “a new genetic underclass that does not discriminate by race.” A victim of genoism. As he points out in the film, “What began as a means to rid society of inheritable diseases has become a way to design your offspring—the line between health and enhancement blurred forever. Eyes can always be brighter, a voice purer, a mind sharper, a body stronger, a life longer.”

  Some people watched that movie and shuddered. I wasn’t among them. There are many worrisome possibilities about the future, questions of privacy, equity, and personal choice not least among them. Even the most ethically complex issues can be framed positively, though, provided we are willing to discuss them. There is no reason why the past has to become the future.

  “Terrible crimes have been committed in the name of eugenics. Yet I am a eugenicist,” the British developmental scientist Lewis Wolpert has written. “For it now has another, very positive, side. Modern eugenics aims to both prevent and cure those with genetic disabilities. Recent advances in genetics and molecular biology offer the possibility of prenatal diagnosis and so parents can choose whether to terminate a pregnancy. There are those who abhor abortion, but that is an issue that should be kept quite separate from discussions about genetics. In Cyprus, the Greek Orthodox Church has cooperated with clinical geneticists to reduce dramatically the number of children born with the crippling blood disease thalassemia. This must be a programme that we should all applaud and support. I find it hard to think of a sensible reason why anybody should be against curing those with genetic diseases like muscular dystrophy and cystic fibrosis.”

  You don’t have to be Dr. Frankenstein to agree with him. We need to address these issues and others we have yet to envision. There will be many ways to abuse genomics. The same technologies that save and prolong millions of lives can also be used to harm people and discriminate against them. But hasn’t that always been true? The stakes are higher now, but the opportunities are greater. We are still in control of our fate, although denialists act as if we are not. The worst only happens when we let it happen.

  6

  Surfing the Exponential

  The first time Jay Keasling remembers hearing the word “artemisinin”—about a decade ago—he had no idea what it meant. “Not a clue,” Keasling, a professor of biochemical engineering at the University of California at Berkeley, recalled. Although artemisinin has become the world’s most important malaria medicine, Keasling wasn’t up on infectious diseases. But he happened to be in the process of creating a new discipline, synthetic biology, which, by combining elements of engineering, chemistry, computer science, and molecular biology, seeks nothing less than to assemble the biological tools necessary to redesign the living world.

  No scientific achievement—not even splitting the atom—has promised so much, and none has come with greater risks or clearer possibilities for deliberate abuse. If they fulfill their promise, the tools of synthetic biology could transform microbes into tiny, self-contained factories—creating cheap drugs, clean fuels, and entirely new organisms to siphon carbon dioxide from the atmosphere we have nearly destroyed. To do that will require immense c
ommitment and technical skill. It will also demand something more basic: as we watch the seas rise and snow-covered mountaintops melt, synthetic biology provides what may be our last chance to embrace science and reject denialism.

  For nearly fifty years Americans have challenged the very idea of progress, as blind faith in scientific achievement gave way to suspicion and doubt. The benefits of new technologies—from genetically engineered food to the wonders of pharmaceuticals—have often been oversold. And denialism thrives in the space between promises and reality. We no longer have the luxury of rejecting change, however. Our only solutions lie in our skills.

  Scientists have been manipulating genes for decades of course—inserting, deleting, and changing them in various molecules has become a routine function in thousands of labs. Keasling and a rapidly growing number of his colleagues have something far more radical in mind. By using gene sequence information and synthetic DNA, they are attempting to reconfigure the metabolic pathways of cells to perform entirely new functions, like manufacturing chemicals and drugs. That’s just the first step; eventually, they intend to construct genes—and new forms of life—from scratch. Keasling and others are putting together a basic foundry of biological components—BioBricks, as Tom Knight, the senior research scientist from MIT who helped invent the field, has named them. Each BioBrick, made of standardized pieces of DNA, can be used interchangeably to create and modify living cells.