Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives - Michael Specter (2009)

Chapter 5. Race and the Language of Life

In the spring of 1998, a team of researchers from the Centers for Disease Control traveled to a meeting of the American Thoracic Society in Chicago, where they presented a report on the severity of asthma among Hispanics. Minorities living in America’s largest cities visit the emergency room more often, spend more time in the hospital, and die in far greater numbers from asthma than the rest of the population; they are also far more likely to develop pneumonia and other pulmonary diseases. None of that was news to most of those who attended the meeting, but the CDC study was the first to focus specifically on the prevalence of asthma in Hispanics. During the course of his presentation, the pulmonary specialist David Homa pointed out that he and his colleagues had run across one particularly surprising result in their research: Hispanics living in the Northeast of the United States were three times more likely to develop asthma than Hispanics in the South, Southwest, or West.

Many people in the audience found that odd; differences in the rates of pulmonary disease are often a result of social conditions, the environment, and disparities in the quality of health care. Poor people rarely receive the best possible treatments and consequently they don’t do as well as richer patients—with asthma or with most other illnesses. The study was designed to account for those facts. Even so, a Hispanic man in New York was more likely to get sick than one in Los Angeles or Chicago. Some participants shook their heads in surprise when they saw the data, but Esteban González Burchard was not among them. Burchard, at the time a twenty-eight-year-old internal medicine resident at Boston’s Brigham and Women’s Hospital, had known for years that he wanted to specialize in pulmonary disease, largely because of its punishing effect on minorities. He sat riveted by Homa’s presentation, and particularly by the data that suggested the illness seemed so much worse on the East Coast than in other parts of the United States.

“I jumped when I heard him say that,” Burchard told me when we first met in his office at the University of California at San Francisco, where he is assistant professor in the departments of biopharmaceutical sciences and medicine. “I am Hispanic and I have lived on both coasts and I knew that the obvious difference there had to be between Puerto Ricans”—who reside principally in the East—“and Mexicans”—who are more likely to live in the West. At the time, Burchard was working in the laboratory of Jeffrey Drazen, a professor at the Harvard School of Public Health, who was soon to become editor of the New England Journal of Medicine. In his lab, Drazen had identified a genetic risk factor that would explain the differences in asthma severity between African Americans and Caucasians. Both he and Burchard thought the CDC data might help explain genetic differences within the Hispanic community as well.

“I talked to David Homa and suggested that this data could very possibly be the result of genetics,” Burchard said. “I don’t know if he thought I was a little crazy or what.” After all, genetics seemed unlikely to provide an explanation for such a striking disparity among people with a common ethnic heritage. The prevailing view since the early days of the Human Genome Project has been that such differences no longer seem worth thinking about, and many notable researchers have argued that focusing on race in this way is not only scientifically unsound but socially dangerous. Yet something had to account for the wide gap, so Burchard persuaded Homa that the CDC ought to take a closer look at the data. Two years later, the CDC study, now focusing on the differences among Hispanics of Cuban, Puerto Rican, and Mexican descent, was published. It showed that the prevalence, morbidity, and mortality rates of people with asthma varied significantly within those groups and concluded that genetics seemed to be at least partly responsible.

Burchard, like most physicians, believes that social and economic disadvantages explain much about why minorities in the United States suffer disproportionately from so many diseases—eight times the rate of tuberculosis as whites, for example, ten times the rate of kidney failure, and more than twice the rate of prostate cancer. Tuberculosis has served for generations as the signature disease of urban crowding, homelessness, and poverty, and many people who die of AIDS do so because the virus makes them susceptible to infections that cause pneumonia. But Burchard asked himself whether economics and environment alone could explain why one group of Latinos (Puerto Ricans) had among the highest rates of asthma in the United States while another group (Mexicans) had virtually the lowest. That made no sense. “I was convinced then, and am even more convinced now,” he told me, that “there are specific ethnic, genetic, and environmental risk factors in play here.” For the past decade, Burchard has worked with one principal goal in mind: to understand the meaning of such genetic differences between racial groups. It has not been easy, nor has the research always been particularly welcome. Grant money has often been hard to find, and skepticism from colleagues palpable. But Burchard persisted.

In 2001, with the help of senior scientists from medical centers in the United States, Mexico, and Puerto Rico, he embarked on an exhaustive attempt to better understand the clinical, genetic, and environmental differences in severity among Mexican and Puerto Rican asthmatics. The investigative study, called GALA—Genetics of Asthma in Latino Americans—has not only revealed genetic differences within Hispanic populations. Perhaps more importantly, it has demonstrated that despite having more severe asthma, Puerto Ricans respond less well to the standard treatments they are most likely to receive. Albuterol, for example, is the most commonly prescribed asthma medication in the world, and frequently the sole drug people receive (or need) to treat their asthma. Yet for many Hispanics it can prove useless. Nonetheless, albuterol is often the only asthma drug prescribed for Puerto Ricans or Mexicans in the United States.

“The idea has become fashionable that we are all one species and that ethnicity and race do not play defining roles in determining the causes of disease,” Burchard said. “But look at the data. The one-size-fits-all approach to medicine and to drug therapy does not work. We see that over and over again. I can’t think of anything more important in medicine right now than trying to tease out the causes of these differences. But believe me, there are many people who think I am wrong.” He sat back, shook his head, and smiled darkly. “There are serious scientists who say we should not even do this kind of research, that races should be treated as one and that the genetics of humanity are not diverse enough to play this kind of role in diseases. You can’t look at the data and make those assumptions,” Burchard said. “But if reality upsets people, they will simply look in another direction. People deny what makes them uncomfortable, and many—even in my business—say we shouldn’t use the word ‘race’ at all.”

It has never been easy to invoke the subject of race in America. Discrimination has long been as obvious in medicine as in other areas of society. In the era of personalized medicine, where relevant new information seems to appear daily, the issue has become more volatile than ever. At many meetings where race and genetics are discussed, researchers spend as much time debating semantics as they do discussing scientific results. (In 2008, one participant at a National Institutes of Health conference on genomics and race argued that not only is the term “race” unacceptable, but so is the term “Caucasian,” because it implies racial rather than geographic ancestry.)

“How much of a factor does genetics play in these research results?” Burchard continued. “I will tell you honestly, I don’t know—but neither does anyone else. I am Hispanic and I want people to get the treatment that serves them best. I want every tool at my disposal and every tool at the disposal of my patients. Genetics is one of the most powerful weapons we have. Yes, we are strikingly similar in many—even most—ways. But genetics also makes us different. That scares some people, but it is a fact.

“We are finally coming to a period in scientific history where people may be able to benefit from those differences. Where they can actually help treat and cure diseases. You would think that is something that scientists would support. But too often it is not. Let’s face it, in this country there have been major efforts, guided by endless waves of political correctness, to close the door to the possibility that there could be important racial differences among human beings. At first I found it surprising. I don’t anymore. But be honest: who can possibly benefit from this approach to medicine?”

ON JUNE 26, 2000, surely one of the most notable days in the history of science, President Bill Clinton announced the completion of the first draft of the Human Genome Project. He spoke in the East Room of the White House, where Thomas Jefferson and Meriwether Lewis had presented the map of Lewis and Clark’s historic expedition to the public. The symbolism was impossible to ignore, as were the parallels between what Clinton described as Clark’s “courageous expedition across the American frontier” two centuries earlier and the Human Genome Project’s exploration of the contours and complexities of the human cell. Many of the scientists who had struggled to compile that blueprint of human DNA—the string of three billion pairs of chemical “letters” that make up our genetic code—stood by the president’s side. “Without a doubt, this is the most important, most wondrous map ever produced by humankind,” Clinton said. “We are learning the language in which God created life.” British prime minister Tony Blair, joined the conference by satellite, along with researchers who had contributed to the work in England. Science, Clinton said, was on the verge of gaining immense power to heal, power that until recently we could not have imagined. He noted that the information packed into the structure of our genome was so valuable, and the potential benefits of understanding it so great, that it was conceivable that “our children’s children will know the term cancer only as a constellation of stars.”

That’s unlikely, but Clinton’s optimism hardly seemed misplaced, and it seems even less so now. By assembling a complete map of the human genome, and then refining it literally every day, geneticists have already transformed fields as diverse as anthropology, history, molecular biology, and virology.

An entire industry, genomics, has emerged to study the structures and functions of genes and how they interact with each other. The hereditary information contained within our genes, our DNA, is written in a four-letter language that, if printed out, would fill more than a thousand New York City telephone books. (Each letter corresponds to one of four nucleotide bases: A for adenine, T for thymine, C for cytosine, and G for guanine.) These sequences, arranged in millions of threadlike helixes and passed from one generation to the next, carry within them the instructions required to assemble all living things—a set of instructions which genomic scientists are working feverishly to decode.

The resemblance among humans is startling: compare one person with any other, chosen randomly from any two places on earth, and genetically they will be more than 99 percent identical. It doesn’t matter whether one of those people is from Sweden and the other from Zambia, or whether they are twins, or of different genders. Yet, there are still millions of places in our genome where that recipe varies among individuals by just a single genetic letter. Those places are called single-nucleotide polymorphisms, or SNPs (pronounced “snips”). SNPs are useful markers for different versions of genes, and they help emphasize the differences that scientists are trying—with increasing success—to associate with various diseases. Over the past decade, researchers have been able to use these surrogates as molecular guideposts to identify scores of genes that play major roles in diseases ranging from prostate cancer to age-related macular degeneration.

The Human Genome Project launched a modern Klondike, and billions of dollars have been invested in an attempt to understand the exact structure of virtually every gene in the human body and then translate that knowledge into effective drugs. We are in the earliest stages of this vast effort at sifting through the raw data that contains the language of life. Eventually, however, genomics will almost certainly provide the information necessary to help answer many of the most fundamental questions we can ask about ourselves and about biology. To what extent are genes responsible for how we grow, think, evolve, become sick, and die? Are traits that pass through generations in a community genetically determined, or are they the expression of cultures that have been shared for thousands of years? Is it even possible to quantify how much of what we are comes from genes and how much from the circumstances of our lives?

The last question is the most important because when we understand how humans are put together we will have a much better grasp of the genetic basis of major diseases—what causes them and what causes people to vary so dramatically in their ability to respond to particular medicines. As every physician knows, drugs that work well for one person don’t necessarily work for others. Some, like albuterol, are effective on whites but not on many Hispanics. For African Americans, who suffer from congestive heart failure at twice the rate of whites, there is BiDil—a combination of two older drugs, which when taken in concert turn out to work far better for blacks than for whites. (The drug, when used in this fashion, became the first race-based medicine approved by the FDA, specifically to treat blacks. The action caused intense controversy, but it also offered a new form of relief to African Americans with heart failure.)

While vital clues to causes of various afflictions emerge in a torrent, they rarely provide definitive answers. But the initial map did prove conclusively that all humans share a nearly identical genetic heritage. Many researchers have even argued that relying on race as a way to define and connect large groups of seemingly similar people no longer makes sense, except as a way to discriminate against them.

President Clinton made a point to stress that at his news conference. After all, what could be more exciting to a liberal politician raised in the South than unshakable evidence that racism was based on a series of socially created misconceptions about human evolution? As Eric Lander, a genomic pioneer and the director of the Broad Institute, the research collaboration between Harvard and MIT, put it, “Racial and ethnic differences are all indeed only skin deep.”

J. Craig Venter, who at the time was president of Celera Genomics, the private company that dueled with the government to complete the project first, also attended the ceremony. There is no more compelling or astute scientist in the world of genomics than Venter, who in 1992 founded the Institute for Genomic Research. A comment he made that day, that “the concept of race has no genetic or scientific basis,” has been repeated often. So have the remarks of his main competitor, Francis S. Collins, the renowned geneticist who led the federal effort to map the genome, pointed out that the data showed there were probably more significant genetic differences within racial groups than between them. (In 2009, Collins was named by Barack Obama as director of the National Institutes of Health.) All those comments provide support for the comforting idea of a family of man, even a society without race.

Nor should such findings be surprising; we are a young species, one that migrated out of Africa and throughout the world only about one hundred thousand years ago—relatively recently in evolutionary terms. Many scientists already understood this well. In fact, during the first decade of the Human Genome Project some participants were so convinced of the homogeneity of humanity that they insisted that the genomic sequence of any one person could be used as a basic reference template for everyone else on earth.

There was a widely shared feeling, according to M. Anne Spence, who was on the Genome Project’s ethics committee, that the sequences would be the same and that gender ought not to matter. Spence and several others insisted that such thinking made no sense. For one thing, men carry a Y chromosome and women two Xs. That would have to account for some differences. Nonetheless, most drug research in America has been carried out on middle-aged white men. People often have radically different responses to the same medicines—and women, in particular, react in ways that men do not. Spence pointed that out and also argued that sequencing the genome was not simply a scientific enterprise, but one with lasting implications for our political, social, and cultural lives.

She may have been more right than she knew. In its early days, instead of settling debates about race and medicine, the Genome Project inflamed them. By the time the genome was published, nearly a year after Clinton’s announcement, two distinct camps had formed: those who believed race no longer existed as a biological entity, and those who argued that race and ethnic background continued to provide crucial information for medical research. Debates erupted in scientific journals, at academic conferences, on university campuses, and even within the federal government’s scientific establishment. Considering the term’s origins, the anxiety is not hard to understand. Classifying people by race has had a profoundly disturbing history, leaving a legacy of hatred throughout the world. Naturally, then, many scientists rushed to embrace our remarkable genetic similarities as a way to dismiss race entirely. As Robert Schwartz of Tufts University argued in a widely circulated article published in the New England Journal of Medicine, “Race is a social construct not a scientific classification.”

He went on to point out that racial identification plays its most important—and destructive—role in setting social policies. In one way or another race has been used to justify much of the abuse humans have inflicted on each other throughout history. Putting race together with medicine has been particularly explosive. One has only to think of the Tuskegee Experiment to see that. Race has been used to justify eugenics, and more than once to justify genocide. The facts of the human genome suggested that it might be possible to move beyond such divisive ways of thinking about our species. “Sadly,” Schwartz wrote, “the idea of race remains ingrained in clinical medicine. On ward rounds it is routine to refer to a patient as black, white, or Hispanic yet these vague epithets lack medical relevance.”

Most scientists think it will be years, possibly decades, before we reap the full intellectual harvest of the Human Genome Project. After comprehensive study, we can explain a small percentage of genetic links to common disease. But there is much more we don’t understand—including how some genes work to protect us from illnesses that other genes cause. Meanwhile, that 99 percent figure has been published everywhere and is used as the basis of a propaganda war by both sides in the race debate. There is no disputing our homogeneity. It is also true, however, that we share 98.4 percent of our genes with chimpanzees. Few people would argue that makes us nearly identical to them. Even drosophila—the common fruit fly—has a genetic structure that shares almost two-thirds of its DNA with humans. Does that mean we are mostly like fruit flies? The simple and largely unanswered question remains: what can we learn from the other 1 percent (or less) of our genome that sets us apart from everyone else?

“WHAT WE ARE going to find is precisely that the other percent plays a role in determining why one person gets schizophrenia or diabetes while another doesn’t, why one person responds well to a drug while another can’t tolerate it,” Neil Risch said. Risch, who is Lamond Distinguished Professor and director of the Institute for Human Genetics at the University of California at San Francisco, argues that the concept of race remains highly valuable in medicine, and that people only pretend otherwise out of a misguided sense of decency. “It’s crazy to banish race just because it makes people uncomfortable,” he said. “It’s a genuinely nice idea and I understand the reasons for it. But scientifically it just makes no sense.

“These are imperfect but valuable ways to describe a group,” he continued. “You can talk about age in the same way. Rarely would a person’s chronological age correspond exactly with his biological age—for both environmental and genetic reasons. Using a birth year is not necessarily a precise way to measure it. We all know there is ageism in society. Does that mean as physicians we should ignore a person’s date of birth? Of course not. It’s an important tool in our arsenal.”

Risch is one of the most prominent and highly respected geneticists in the United States, and when it comes to this issue, one of the most controversial. He is also antsy; when we met in his office he would sit quietly for a few moments, then burst into speech and then abruptly stop. “Here’s the deal,” he said, “especially for complex major diseases. You see differences in health rates and is your first conclusion going to be that they are based on genetics? Of course not. Inevitably, the environment is playing some role and the interaction between environment and genetics is incredibly complex.

“If you go to morbidity and mortality statistics, what do you find?” he continued. “You find that African Americans generally have higher rates of disease and death across the board for everything; all cancers, heart disease, just about everything. This just doesn’t make sense genetically. The differentiation between racial groups is not big enough for one group to have all the genes for disease. So of course it’s environmental.” He smiled, pausing for emphasis. “But when you eliminate the environmental differences you are still left with a significant disparity between races, and there is where genetic factors may play more of a role.”

Risch rattled off a list of diseases in which genetic variations between ethnic groups had been observed: Crohn’s disease is more common in people of European heritage, and Risch’s team identified a SNP that confers a much higher risk on Europeans than on any other geographical group. “This is clear and unequivocal,” he said. “Those SNPs don’t exist in Asians or in Africans. There are others. Hemochromatosis”—a condition in which the body produces and stores too much iron. “Between 8 and 10 percent of Europeans have this mutation. In the rest of the world, though, it is almost nonexistent.” Perhaps the most interesting example is of a particular protein used by the AIDS virus to dock with cells and infect them. The Delta 32 mutation on the CCR5 receptor prevents that; the virus can’t find a convenient way to lock on and infect cells that carry this mutation, which is present in as many as 25 percent of white people, particularly in northern Europe. The mutation has never been found in Africans or Asians.

“There are real, powerful, and useful implications to all this,” Risch said. “Interferon is a treatment used for hepatitis C. Forty percent of Caucasians respond well to it and actually clear the virus out of their system. Africans don’t respond at all. Not at all. This matters immensely. It’s not socio-cultural or economic. It seems to be genetic. And we need to know this, because giving blacks interferon when they have hepatitis C is not going to help them. We have to come up with other treatments.”

Late in 2008, the National Human Genome Research Institute held a forum at which genetic researchers discussed with ethicists how best to present their discoveries to the public. Studies that underscore racial differences are almost always in dispute. In 2005, the geneticist Bruce Lahn and colleagues at the University of Chicago published two papers that described their investigations into the evolution of the human brain. Lahn found that mutations in two genes that regulate brain development were more common in Eurasians than in Africans. That implies that those variants conferred a survival or reproductive benefit, and that they emerged after humans left Africa.

Nobody knows what those genes do, and there was no evidence to show that they had acted on intelligence. Nonetheless, putting the words “gene,” “brain,” and “race” together in a sentence is bound to cause trouble. People on both sides of the political divide leapt to conclusions; Lahn, a lifelong liberal, was embraced by the right and denounced as a sensationalist even by some of his colleagues. He had stressed that the study had no racial component per se, and that genes other than those in the brain could have caused their selection. Nor is it clear what, if anything, those mutations represent. But because they were less common among sub-Saharan Africans than in other populations, the work caused a sensation. Still, Lahn has wondered for years whether there might be a genetic element to variations in social status. “You can’t deny that people are different at the level of their genes,” he said at the time, citing the examples of skin color and physical appearance. “This is not to deny the role of culture, but there may be a biological basis for differences above and beyond culture.”

That kind of talk infuriated his colleagues, and it still does. At the NIH workshop, Celeste Condit, a professor of speech communication at the University of Georgia, spoke about the way she thought Lahn’s study was framed. “The papers could be seen as having a political message,” Condit told Science magazine: in other words, the research might have implied that those genes contribute to differences in IQ. Lahn, who has since shifted the focus of his work to stem cell research in part because of the controversy, has repeatedly stated he had not meant to suggest that.

During the bicentennial celebration of Darwin’s birth, in 2008, the journal Nature invited distinguished scientists to debate whether the subject of race and IQ was even worthy of study. The dispute was lively. “When scientists are silenced by colleagues, administrators, editors and funders who think that simply asking certain questions is inappropriate, the process begins to resemble religion rather than science,” Stephen Ceci and Wendy M. Williams, geneticists at Cornell University, wrote. “Under such a regime, we risk losing a generation of desperately needed research.” The British neuroscientist Steven Rose disagreed funde mentally, calling the study of the relationship between race and IQ “ideology masquerading as science.”

Despite the subject’s volatility, and the fact that most people would prefer to deny its implications, neither the federal government nor the pharmaceutical industry is quite ready to abandon the concept of race. In March 2008, the National Institutes of Health announced the establishment of the Center for Genomics and Health Disparities. (If there were no genomic disparities, why establish such a center?) A few months earlier, the Pharmaceutical Research and Manufacturers of America had released a lengthy report describing nearly seven hundred new drugs that were under development to treat diseases that disproportionately affect African Americans. (There was more than a little marketing behind the report; many of those drugs, should they make it through the FDA approval process, would also prove beneficial for other ethnic groups.)

Some of the genetic factors involved in drug response have been known for decades and can be attributed to proteins called drug metabolizing enzymes. Differences in the genes that encode these molecules are responsible for how quickly the enzymes process and eliminate drugs from our bodies, as well as how they are broken down in the blood. If a drug is metabolized too quickly, it may not reach a high enough concentration to work properly. If it is metabolized too slowly, however, enough of that drug could accumulate to reach a toxic level in the body. In either case, the patient would suffer, but none of that is news to physicians with ethnically diverse patient populations.

“Almost every day at the Washington drug clinic where I work as a psychiatrist, race plays a useful diagnostic role,” Sally Satel wrote in a much-debated 2002 New York Times article entitled “I Am a Racially Profiling Doctor.” She has written often about the subject. “When I prescribe Prozac to a patient who is African-American, I start at a lower dose, 5 or 10 milligrams instead of the usual 10-to-20 milligram dose. I do this in part because clinical experience and pharmacological research show that blacks metabolize antidepressants more slowly than Caucasians and Asians. As a result, levels of the medication can build up and make side effects more likely. To be sure, not every African-American is a slow metabolizer of antidepressants; only 40 percent are. But the risk of provoking side effects like nausea, insomnia or fuzzy-headedness in a depressed person—someone already terribly demoralized who may have been reluctant to take medication in the first place—is to worsen the patient’s distress and increase the chances that he will flush the pills down the toilet. So I start all black patients with a lower dose, then take it from there.”

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 sure. 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.”

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 APP, 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.