For those of you who have been following my argument in this book, that our biology is mismatched with our culture, it’s clear that selecting the genetic traits in our children might be leading us further in the same direction we have been headed in for the past 10,000 years—only much more quickly. As Francis Galton, the father of eugenics, argued in his century-old quote at the head of this chapter, we are simply doing what nature (or culture) has done for many, many years. Using our knowledge of genetics, we will be able to select for traits that will further adapt us to the culture we have created. While the lactase persistence variant that Pritchard analyzed in Chapter 1 may have taken thousands of years to increase to its present high frequency in milk-drinking populations, in theory we can accomplish a similar feat in a few generations—or even a single generation, if applied universally—using new genetic diagnosis techniques. Although these decisions may seem very personal, motivated by parental love and the desire for a healthy child, in fact they have a much larger effect. This is because by selecting for certain traits we are not merely affecting our child but also all of his or her offspring. In the same way that the transgenerational power of developing agriculture during the Neolithic period set in motion forces that would play out over thousands of years, so too will choosing the genes of our children. In effect, we will become the agent of selection for future generations. Such a statement may sound extreme, but it is nonetheless true; once genetic variants are removed from a population, either by natural or artificial selection, only additional mutations can reintroduce them. And that raises the specter of where this may be leading us.
CAREFUL WHAT YOU WISH FOR
The great jazz saxophonist Charlie Parker lived during a golden time in music history—what is commonly known as the “bebop era,” lasting from 1945 to 1960. Parker and his fellow musicians created a revolutionary new form of music, characterized by lengthy improvised sections in the middle of an otherwise composed piece of music. Skillful improvisations are the hallmark of the great jazz musicians of this period, who included legends such as Miles Davis, Thelonious Monk, and John Coltrane. Parker, as with many of his fellow jazzmen, took great pride in living the life of “sex, drugs, and rock ’n’ roll,” as it would come to be known in the 1970s. He may have taken it to extremes, though. According to the psychologist Geoffrey Wills, in a 2003 paper published in the British Journal of Psychiatry, he “consumed enormous quantities of food, used heroin in increasing amounts, was known to drink 16 double whiskies in a 2-hour period and entered into hundreds of affairs with women.” Art Pepper, another jazz great from the period, was quite explicit about his own appetites: “I always prided myself on being able to stay up longer than anybody else, drink more than anybody else, take more pills, shoot more stuff, or whatever.”
These men were not anomalies. According to Wills, the vast majority of great jazz musicians from this period succumbed to drug addiction, alcohol abuse, schizophrenia, bipolar disorder (manic depression), or some other serious mental ailment. The most common factor in these problems, according to Wills, was disinhibition—the lack of a behavioral “edit” mechanism, by which most people limit their activity to what is generally thought to be healthy and socially acceptable. Perhaps not surprisingly, a recent study by Charles Limb of Johns Hopkins and Allen Braun of the National Institutes of Health that used magnetic resonance imaging to peer into active brains showed that the part of the brain involved in inhibition is turned off in improvising jazz musicians. Perhaps being able to turn this part of the brain off is what allowed the greats to become so good at this critical skill, and this characteristic extended into other parts of their lives as well, leading to drug abuse and promiscuity.
Similarly, many great artists and writers have been prone to alcoholism and other mental disorders. Manic depression has been linked to high levels of creativity, as detailed by Arnold Ludwig in his book The Price of Greatness. Overall, there seems to be a correlation between mental illness and creativity that goes beyond the merely anecdotal. It’s as though either something about the act of creation predisposes a person to such problems or, perhaps, that having such a predisposition leads to greater creativity. Just like sickle-cell anemia, where a genetic variant that is bad in one context can be good in another, it’s possible that the genetic variants that predispose a person to mental disorders may also foster the type of nonlinear thinking that leads to great artistic accomplishments.
The psychologist David Horrobin, in his book The Madness of Adam and Eve, does, in fact, argue that the genes for schizophrenia are the same as those that produce creativity. While this model has not been widely accepted, he does make a compelling case for the oddly similar incidences of schizophrenia in worldwide populations. Around 1 percent of people, regardless of ethnic background or geographic origin, are schizophrenic, whereas most other human diseases vary widely in their population incidences. He suggests that this is because schizophrenia results from having too many copies of “creativity genes” that, in smaller numbers, are useful and have been selected for in human populations because of their beneficial effects. In other words, if you have one or two copies of genetic variants that predispose you to schizophrenia, you might also be predisposed to become a great composer or mathematician (or, to put it in the context of our Paleolithic ancestors, better at developing new tools or anticipating where to find food); having three or four, however, could tip you over the edge to schizophrenia. Again, such a model is highly speculative, but it would explain both the relationship between mental illness and the creative process and why all human populations exhibit schizophrenia. Dr. Navratil, from the House of Artists, certainly would have agreed with Horrobin.
But what might happen in a future where such variants are routinely selected against? After all, most parents wouldn’t wish a debilitating illness like bipolar disorder or schizophrenia on their children. In so doing, however, might they also be selecting against creativity? While such a one-to-one correspondence between genetic predisposition and ultimate outcome vastly oversimplifies the complexity of human behavior and psychiatric disorders, it is likely that extreme creativity has at least a partial genetic basis. Perhaps creativity is a knife edge, on which we sit poised to teeter in the direction of either illness or accomplishment—and, indeed, many creative people alternate between the two. In an effort to avoid the former, could we also be deterring the latter? After all, at its core, creativity is imagining things that aren’t there and then making them real. Schizophrenia is largely defined by such vivid imaginings, although to such an extent that it becomes deleterious to the individual.
Psychology isn’t the only thing we might be able to influence. As we saw with James Neel’s “thrifty genotype” hypothesis, if we select for genetic variants that protect against diabetes, will we also be creating hothouse flowers of ourselves—svelte, calorie-burning humans with metabolisms perfectly adapted to the excessive nutritional intake and low exercise levels of modern industrial society? If so, will we lose our ability to cope with any potential disaster that may befall us in the distant future? As our food supply tends toward an ever greater monoculture of clonal genetic strains, what will happen if the equivalent of the Irish potato famine strikes in several hundred years’ time? Will our distant grandchildren thank us for having molded them into the perfect twenty-first-century biology—one that may lead them to starve in a time of scarce resources?
The real threat of such genetic decisions will, of course, take many generations to be ascertained. The world may change so completely in the next few hundred years that such self-selection will become less important. Perhaps famine really will become a distant memory, and computers will be more creative than humans. But another option, one that manifests itself in genetic changes within our own lifetimes, is now being tentatively applied to people born with terminal illnesses. It is the option of direct genetic modification, and its aim is to eradicate serious illness not by selecting for genetic variants in the next generation but by
substituting a good for a bad gene within a living person. Such treatments, and their potential consequences, raise many questions.
VIRUSES, ANTS, AND REPUGNANCE
W. French Anderson, who was the scientific consultant on the movie Gattaca, leapt to worldwide fame in 1990 when he became the first doctor to treat a genetic disorder with gene therapy. His patient, a four-year-old girl from Cleveland, Ohio, named Ashanthi DeSilva, had a rare disorder known as severe combined immunodeficiency, which is like an inherited form of AIDS in which the person has no functioning immune system. In Ashanthi’s case, it was caused by crippling mutations in both of her copies of the gene for adenosine deaminase (ADA), an enzyme critical for immune function. Anderson inserted a normal copy of the gene into a retrovirus, which was then used to infect a sample of her white blood cells. These modified white blood cells were then transfused into Ashanthi, the goal being to introduce the functioning gene into her genome and overcome the genetic deficit by overproducing a functional copy of the key gene. Although her condition improved dramatically and she’s still alive as of 2009, it has been hotly debated whether the gene therapy or the additional treatment provided by administering extra ADA by injection was responsible—the ethical review board had refused to take the chance of letting the gene treatment work on its own.
The success of Ashanthi’s treatment led to an explosion of applications for additional gene therapy trials. By the end of the 1990s, around three thousand people had received treatment using these methods, but, unfortunately, most weren’t as lucky as Ashanthi. When, in 1999, eighteen-year-old Jesse Gelsinger died of a massive immune response to the adenovirus used to carry a therapeutic gene to his cells, it not only shut down all such work at the University of Pennsylvania but led many people to question the safety of the whole field of gene therapy. If the risks were so significant, was it even worth undergoing a therapy that had a minimal chance of succeeding?
The mixed results of gene therapy expose another case of pleiotropy. In this case, what seemed to work in theory or in the laboratory (though two monkeys given Jesse’s treatment had died of similar complications) simply didn’t work when used in a human being. The multiple levels at which gene therapy components interact with human physiology makes predicting outcomes very difficult. More and more, we are coming to realize that tinkering with nature can produce unintended effects, even if the tinkering seems well planned and justified.
One recent example from a different field was described in a 2008 study published in the journal Science. The researchers were testing different methods of preserving acacia trees on experimental plots in Kenya. Half of the plots were surrounded by fences that excluded herbivores such as elephants and giraffes, while the other half were left open. The thinking was that if herbivores were kept away, at least for a while, the acacia trees—which had become stressed by overgrazing—would have a chance to thrive. Quite the opposite happened, unfortunately; the trees protected from the herbivores became weaker and were actually more likely to die than those left open to the ravages of wandering leaf nibblers. It seems that the trees’ defense system, composed of tiny ants living in their hollow thorns and feeding on nectar produced by the plant, had started to abandon the plot when they were no longer needed and the plants reduced their nectar production. They were replaced by another species of ant that allowed other insects, including a nasty boring beetle, to attack the tree. This simple example illustrates the complex and unpredictable web of interactions among living organisms in a relatively well-understood ecosystem, and the dangers of trying to modify one component without taking into account the effect on others.
We know even less about the complexities of human biology, although we are learning at an incredibly fast pace. Still, the biggest gap in our knowledge of ourselves is how the genome is translated into a living system. How do genes get turned on and off at the right levels to produce the biochemical mix in our cells, and how do these cells know how to work together to produce tissues, and how do tissues regulate themselves to create a viable organism? Then there is the question of consciousness, which is still not understood. Overall, the system is so incredibly complex that the mind boggles at how it all manages to work together. The answer is that billions of years of evolution have optimized the functions of all of these components until they work in harmony most of the time, except in rare cases where severe diseases result from seemingly trivial changes.
All of this complexity has led many people to question the ultimate utility of human genetic modification. While in theory many things may be possible using these techniques, for most people the risks will greatly outweigh the benefits. The bioethicist Leon Kass has written about what he calls “the wisdom of repugnance,” where there is a subconscious sense of what is right and wrong in cases of biological modification. Although he first applied it to a discussion of human cloning, it could equally apply to other genetic modifications. Kass’s argument has been criticized by many in the scientific community as a Luddite response, since all sorts of things that once seemed repugnant to many people—divorce, abortion, homosexual unions—are now commonplace. But as a brake on the unfettered application of all new scientific discoveries, Kass’s guideline is perhaps a useful initial litmus test. Ultimately, though, the question of whether to apply these techniques should be part of a society-wide debate, not simply left up to physicians and their patients, egged on by pharmaceutical companies. Society, in turn, needs to become better educated about the risks and benefits inherent in such technologies. In a world where even physicians can make statements like “Charlie Whitaker should simply accept his fate,” fewer than half of American adults can define DNA, and fewer than half of U.S. adults accept evolution, scientists clearly have a lot of work to do in communicating scientific concepts to a broader audience.
Overall, the debate should be about not what we are capable of doing but what we should be doing. As we move ever more quickly into a future that is a far cry from our origins as a species, we should take care to preserve what is important about being human. The most obvious choice in the twenty-first century may be to “pop a pill”—including one that changes your DNA—but we should always try to bear in mind what the long-term consequences might be. Certainly, we are clever enough to develop any number of new tools, including medical interventions, but are we wise enough to use them properly? There is a clear danger inherent in modifying the genes of the next generation, or our own, when we still don’t understand enough about interactions and risk. Short-term thinking may lead us down a path that seems to offer infinite hope at the time but ends up with a nasty sting in the tail hundreds of years later.
Although the genetic possibilities in this chapter may still seem quite futuristic, and it will take us many generations to assess their ultimate impact, another such scenario is now playing out beyond biology. Decisions made nearly two centuries ago about fuel sources, egged on by our increasing appetite for energy, have led to an unprecedented impact on the natural world. Humans, armed with a desire for novelty and mobility, have used fossil fuels to take a ride. And now these same fuels may be returning the favor, in the form of a human-induced change in climate unlike any the world has seen in recent memory. Like the ice age returning at the onset of the Younger Dryas, and all that it meant for shifts in human behavior, climate change may already be impelling us toward a destination that will challenge what we think we know about human society and the world we live in. And as a model for the unquestioning acceptance of new technology, the story should serve as a warning for powerful technologies such as genetic engineering. Next stop: the South Pacific, and the leading edge in the battle over global warming.
Chapter Six
Heated Argument
It is not the strongest of the species that survives, nor the most intelligent, but rather the one the most adaptable to change.
—ATTRIBUTED TO CHARLES DARWIN
TUVALU
The silence on the plane was almost deafening, psychologi
cally blocking out the drone of the twin propellers. I was crusty with dried sweat, uncomfortable from having spent half a day standing on boiling-hot tarmac, waiting for the pilots to get the engines started on the fifty-year-old Convair aircraft. Without an engineer present, they had had to call New Zealand via satellite phone for step-by-step instructions on how to fix the problem. Finally, after tinkering for hours (during which we had wandered back and forth from the airport to the bar in the country’s only hotel), the pilots tried one last time to turn over the right engine before the battery died. It worked, and everyone exhaled in unison. We piled back onto the plane with less than an hour to go until sunset, pleased to be getting out before—because there were no runway lights—darkness grounded us for the night. Each of us worried for a few minutes about whether we would make it the two and a half hours back to Fiji across a huge stretch of open ocean—no emergency landing strips if anything went wrong—but then settled in for the trip.
The reason for the silence, though, was not worry about the safety of the aircraft. Rather, it was shock over the dead woman wrapped in blankets and strapped to one of the front seats. About half an hour after our takeoff from Funafuti Atoll, the main island of Tuvalu, she had collapsed in a heap on the floor. A team of Australian doctors who had been in Tuvalu for the past two weeks immediately leapt into action, attempting to resuscitate her for nearly half an hour. Unfortunately, despite their best efforts, she had been killed by a blood clot in the brain before her slumped body even left the seat. Halfway to Fiji, with no way to return to Funafuti because of the darkness, the crew covered her up and strapped her into her seat, and we continued on our way. Everyone sitting in the forward half of the plane was witness to the whole ordeal, and word quickly circulated among all of the passengers: a woman had died on board.
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