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.”
Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives Page 18