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

by Michael Specter

  The main argument against relying on race in this way is simple but powerful: different races receive decidedly different standards of health care in the United States, and that is unacceptable. The disparity explains why African Americans and Hispanics have more chronic illnesses than whites, and why they take longer to recover from them. Genetics is only one piece of a puzzle; if we place too much emphasis on it we will invariably continue to neglect more significant reasons for the gulf that separates the health of black and white Americans. You don’t have to be an astute student of the United States, or the history of the modern world, to take such concerns seriously.

  Even so, respect for other ethnic groups cannot alter biological reality. Everyone knows how different we all are from each other. Some of us are dark and some are light, some tall and others short. It’s genetic; we inherit those traits from our parents. In fact, entire industries cater to differences like these: nobody would expect to see Barack Obama wearing the same size suit as Kobe Bryant.

  “Many of my colleagues argue that we should banish the word ‘race’ completely,” Neil Risch told me. “They say let’s use different words. Instead of race we should talk about geographic distribution of ancestors. And that’s completely fine with me; we can call it GOAD. Now, think about that for two minutes, and then tell me: if we described people that way, do you actually believe there would be no ‘goadists’?”

  ICELAND MIGHT SEEM like an odd place to search for answers to complex questions about race and genetics. The country has three hundred thousand residents, all of whom are so genetically similar that telephone numbers are organized by first names in the Reykjavik phone book. A thousand years of volcanic eruptions and other catastrophes have had the effect Darwin would have anticipated: those plagues and natural disasters pruned the population and cut back sharply on the genetic diversity of the island. As a result, the hereditary instructions of the entire nation have passed through a small gene pool for fifty generations.

  There are thousands of illnesses—like cystic fibrosis, sickle-cell anemia, and Huntington’s chorea—whose cause can be traced directly to the mutation in a single gene. They usually follow simple Mendelian patterns of inheritance and run in families. Most major diseases, on the other hand, including cancer and cardiovascular illnesses, which kill millions of people every year, are the result of a complex combination of environmental history, behavioral patterns, and the interaction of hundreds of genes working together in ways that even now we only dimly understand.

  The most direct approach to finding the origins of those diseases is to compare the DNA of people who are sick to the DNA of their healthy relatives (and ancestors). When a group is almost identical, their differences become much more apparent. Those kinds of studies are hard to conduct in a racially and ethnically diverse country like the United States, where ancestors can rarely be traced for more than a few generations. If one group’s cultural heritage, environment, and habits differ from another’s then so almost certainly are the causes of its illnesses. That’s not a problem in Iceland. Despite centuries of seclusion on a remote island in the North Atlantic, people there develop serious diseases at roughly the same rate as people in other industrialized countries. There is no place more ideally suited for research into the genetics of major diseases.

  “What do race and genetics have to do with common diseases?” bellowed Kari Stefansson when I asked to discuss the subject with him. He looked as if his eyes were ready to burst. “Everything, obviously. How can you be stupid enough to ask that question?” We were standing in his office at deCODE genetics, the company he founded in 1996 to mine the genetic heritage of the Icelandic people. Stefansson is six feet five inches tall, dresses almost exclusively in black, and is famously imperious. When he hovers over you and calls you an idiot it makes an impression that doesn’t fade quickly. The first time we met, nearly a decade ago, I couldn’t believe that Stefansson could be so condescending. Since then I have come to regard his conversational manner as a personal trait, like freckles or a twitch. Throughout that time, Stefansson’s self-confidence has never wavered—and that’s not wholly without reason.

  Perhaps more than any scientific institution other than the U.S. National Institutes of Health, which is funded by the federal government, deCODE is responsible for producing a stream of genetic information that promises to change medicine in ways that even a decade ago would not have seemed possible. Almost no day passes without some revelation describing how our genes influence the way we live, behave, get sick, and die. DeCODE has isolated genes that are associated with type 2 diabetes, prostate cancer, heart attack, obesity, and schizophrenia, to name just a few. The company has even unearthed tentative hints at the relationship between fertility and longevity. All by homing in on differences in the DNA of people who are as alike as any group on earth.

  “Differences matter,” Stefansson said, striding into his office with a protein drink in each hand. “They matter enough to cure diseases and save million of lives. Race. Geographical ancestry. Call it what you want. If our work has shown us anything, it ought to be that the even smallest of goddamn differences matter.” Stefansson spent more than a decade at the University of Chicago, where he became a tenured professor of neurology. He returned to Iceland briefly in the early 1990s to run the Institute of Pathology, then the country’s most distinguished scientific research organization. He was restless, though, and for five years moved back to the United States as a professor of neurology and pathology at the Harvard Medical School. It was then, during a brief visit home to conduct research on his specialty, multiple sclerosis, that Stefansson realized Iceland was a genetic jackpot.

  The deCODE building, just a brief walk from the center of old Reykjavik, is crafted from the stark school of Nordic realism, all plate glass and angular bits of steel. It is eerily clean and quiet and the mood seems surreal: perhaps that’s because I have only visited in the middle of winter, when the sun sets before noon, and at the height of summer, when people play chess in the courtyards until four a.m. Despite its unparalleled research success, the company has been badly hurt by Iceland’s economic shipwreck, not to mention some unlucky investment decisions and its own outsized ambitions. DeCODE never saw itself solely as a research center. It intended to become a major biotechnology and pharmaceutical company, but those plans have largely remained unfulfilled.

  Nonetheless, deCODE helped start a revolution. Fueled by the almost unimaginably rapid growth in sequencing power, genomics is beginning to transform the way we think about medicine, and about the rest of our lives. The benefits, particularly drug treatments tailored to individual needs, have been overly hyped, as new technologies always are. In the past, it often took twenty-five years to turn a scientific discovery into a common therapy. (Or longer. The German chemist Adolf Windaus won the Nobel Prize in 1928 for work that helped determine the chemical composition of cholesterol. It took almost a century until that discovery made its way into a class of drugs—statins—now taken by millions of people every day.) Powerful computers and gene sequencing technology are changing all that, supplying the vocabulary necessary to make sense of the digital information contained within each of our bodies—and each of our cells.

  SNPS PROVIDE A useful way to calculate a person’s genetic risks of developing scores of diseases. Yet they are a half-measure, an imperfect substitute for the information that comes from scanning an entire genome—which still costs $100,000. The price won’t stay high for long. (In fact, one company, Complete Genomics, claims it will be able to sequence an entire human genome for $5,000 by 2010.) The cost of combing through billions of bits of DNA has fallen by a factor of more than one hundred thousand in less than two decades. In 1990, as the Human Genome Project got under way, scientists estimated that sequencing a single genome would cost $3 billion. The final bill is hard to calculate, because the figures include the cost of many scientific activities relating to genomics carried out during the thirteen-year-long project. But the total
was far less than the original estimate, and when the project ended in 2001, the team said that they could do it again for $50 million.

  Five years later, the molecular geneticist George Church said he could sequence a genome for about $2 million. The following year, it took two months and less than $1 million to sequence the complete genome of James Watson, who in 1953 discovered the structure of DNA along with Francis Crick. A drop in cost from $3 billion to $100,000 in twenty years is impressive. Time is an even more useful measuring stick: what took thirteen years in 1988 and two months in 2007 will almost certainly take less than five minutes within the next two or three years. Church, who is director of the Lipper Center for Computational Genetics at Harvard Medical School, and holds dual positions at Harvard and MIT, expects to see steeper price declines and the faster sequencing rates that come with them, soon. Church helped develop the earliest sequencing methods, nearly twenty-five years ago, while working in the lab of the Nobel Prize-winning chemist Walter Gilbert.

  “I don’t know whether we can squeeze it down by a factor of one hundred in the next year or so—it’s hard to even guess what the cost will be in five years. But it will be low,” he said. “You just don’t get that kind of change in any other industry.” In 2007, Church embarked on his most audacious undertaking, the Personal Genome Project. He intends to sequence the genomes of one hundred thousand volunteers—he has already sequenced and published the genomes of the first ten. The eventual database will prove invaluable in correlating genomic information with physical characteristics. Researchers will have access to the database at no cost. Naturally, without the rapid evolution of sequencing technology the project would not have been possible.

  “In 1984, thirty base pairs”—thirty rungs on the helical ladder of six billion nucleotides that make up our DNA—“was a good month’s work,” Church told me. “Now it takes less than a second.” Craig Venter, who knows as much about how to sequence a genome as anyone, agrees. “I spent ten years searching for just one gene,” he said. “Today anyone can do it in fifteen seconds.” Indeed, the X Prize Foundation has offered $10 million to the first group that can sequence one hundred human genomes in ten days at a cost of $10,000 or less per genome. As many as two dozen teams are expected to compete.

  In 2007, seizing on the cascade of genetic information that had suddenly become acessible, deCODE and two California companies, 23andme and Navigenics, began to sell gene-testing services directly to consumers. The tests analyze up to one million of the most common SNPs—a small fraction of our genome—focusing on the most powerfully documented relationships between those SNPs and common diseases. For each disease or condition, the companies estimate the risk of a healthy person developing that illness. Both deCODE and 23andme sold their first tests for just under $1,000, but prices keep falling. By the end of 2008, a 23andme test cost $400. Navigenics charges $2,500 for its full regimen, which includes the services of genetics counselors; deCODE offers packages at various prices.

  Much of deCODE’s research relies on its own formidable database, while 23andme, whose slogan is “Genetics just got personal,” has emphasized genealogy and intellectual adventure, not just medicine, and encourages customers to share data, participate in research studies, and form social networks on its Web site. In 2008, Time magazine named the 23andme test as its invention of the year, but critics have described the company’s approach as frivolous because it not only provides disease information but also helps customers learn about less useful—but perhaps more amusing—traits like whether they have dry ear wax or can taste bitter foods. Nobody disputes the quality of the company’s science, however, or its standards. (I should state clearly, and for the record, that the founders of 23andme are close friends of mine, and have been for years.)

  The testing process is similar at each company. After spitting into a tube or swabbing their cheeks for saliva, customers submit samples of their DNA. Within weeks, they receive an e-mail informing them that they can retrieve their information from a secure Web site. These are not diagnostic tests and their predictive value is subject to much debate. Many diseases involve the interaction of scores or even hundreds of genes. A SNP that shows a heightened risk for a particular condition almost always only tells part of the story, and some people worry that since the data is rarely definitive customers might be misled. “We are still too early in the cycle of discovery for most tests that are based on newly discovered associations to provide stable estimates of genetic risk for many diseases,” wrote Peter Kraft and David J. Hunter, both epidemiologists at the Harvard School of Public Health, in an article titled “Genetic Risk Prediction—Are We There Yet?” in the April 16, 2009, issue of the New England Journal of Medicine. They thought not. “Although the major findings are highly unlikely to be false positives, the identified variants do not contribute more than a small fraction of the inherited predisposition.”

  None of the services pretend that genetic tests alone can explain complex health problems. On its Web site, 23andme states that “in order to make a diagnosis, your doctor considers not only your genetic information, but also your particular personal and family history and your physical condition, as well as any symptoms you are experiencing. Your genotype is only part of the equation.” Making a similar point, deCODE suggests that you explore your genetic risk factors and keep a vigilant eye on your prospects for prolonged health. Even Navigenics, the most clinically oriented of the three, tells prospective customers that there are no certain answers in the information they provide: “This level of personalization may help you take action to detect health conditions early, reduce their effects or prevent them entirely.”

  Even knowledgeable consumers can struggle to put partial genomic data into perspective, particularly if a report indicates that they are at greatly increased risk of developing a serious illness. That information is based on what is known—which in most cases is only a fraction of what there is to learn. Three prominent health officials, including the editor of the New England Journal of Medicine and the director of the National Office of Public Health Genomics at the Centers for Disease Control, have suggested that until better data is widely available, a person would do more to improve his health outlook by “spending their money on a gym membership or a personal trainer.”

  Caveats and caution are necessary because risk is relative and few people deal with abstract probabilities rationally. If, for instance, a person has four times the normal risk of developing a particular disease, should he worry? That is an extremely elevated figure. Without context, however, a number means nothing. Take the digestive disorder celiac disease; fewer than one in a hundred people develop celiac disease in the United States, so a relative risk figure four times the average would mean that you stand a slightly greater than 96 percent chance of avoiding it completely.

  That doesn’t mean genomic tests aren’t useful. They can change (and save) your life. Jeff Gulcher, deCODE’s forty-eight-year-old chief scientific officer, wasn’t around the last time I was in Reykjavik. Stefansson and he have worked together for more than two decades, since the day that, as a graduate student, Gulcher walked into Stefansson’s laboratory at the University of Chicago.

  When Gulcher took his deCODEme test, a month before I arrived, he learned that his relative risk of developing prostate cancer was 1.88. That meant he was almost twice as likely as the average person to get the disease. Gulcher took those results to his physician, who ordered a prostate-specific antigen test. PSA is a protein produced by cells of the prostate gland. The results fluctuate, but in general the higher they are, the more likely a man is to have prostate cancer. Gulcher’s test showed that he had 2.4 nanograms of PSA per millimeter of blood, well within the normal range. Those tests are routinely recommended for men fifty years of age and older. But because Gulcher was not yet fifty, most doctors would never have given his results a second thought.

  With Gulcher’s genetic profile in hand, however, his physician scheduled an ultrasound, just to be sur
e. The films revealed an aggressive tumor, though it had not yet spread beyond the prostate. “Jeff was so young that nobody would have made anything of that kind of PSA score for ten years,” Stefansson said, staring into Gulcher’s empty office. “By which time he would surely have been long dead.” Gulcher had surgery, quickly recovered, and returned to work. His prognosis is excellent.

  Gulcher makes his living pondering the meaning of risk. Most people don’t. Critics of the tests say they are still too complex for an average consumer to fully understand. Kari Stefansson disagrees. “That is such bullshit,” he screeched. “We are actually criticized for revealing valuable information to unsuspecting citizens at their request, people who paid for exactly that service. If somebody does not want to know this information he should not have the test done. It’s not required. But it is extraordinarily patronizing to tell a person that he is not mature enough to learn about himself.

  “By the way,” he continued, “in most American states, you can get in a car and use your driver’s license as identification to buy a gun. Then you can drive to a liquor store. You can have the bottle, the gun, and the car. That’s fine. But for heaven’s sake don’t learn anything important about yourself or your family. For some diseases there is no treatment or no useful response yet. But you have to remember that our ability to treat diseases was always preceded by our ability to diagnose them. So our ability to prevent diseases will surely be preceded by our ability to assess risk.”

  That fact is easier to handle in theory than in practice, however. Throughout the early years of the AIDS epidemic many people who had reason to fear they might be infected nevertheless didn’t want to know. At the time, there was no treatment or cure. A positive test was a death sentence with no reprieve. “These decisions are never easy to make,” said Arthur Caplan, the director of the Center for Bioethics at the University of Pennsylvania. “That lag between knowledge and application can be excruciating. Maybe personal genomics will look different in ten years, but right now it’s a world of fortune-telling and bad news.”