Falter: Has the Human Game Begun to Play Itself Out?

by Bill McKibben

  Genetic work on other organisms was under way simultaneously, of course, and some of it was moving much faster. Monsanto figured out how to make lots of crops resistant to herbicides, which allowed farmers to spray more herbicides, which has boosted the bottom line considerably (Monsanto’s, not the farmers’). But for the human organism in particular, there hadn’t been a huge amount to show for the genetic revolution; it was slow work because the tools were lacking. As Michael West, the CEO of Advanced Cell Technology, said, “The dream of biologists is to have the sequence of DNA, the programming code of life, and to be able to edit it the way you can a document on a word processor.”2 As you can tell from the archaic use of the term word processor, he said this quite a while ago—in 2000, to be exact.

  But then CRISPR happened. First, Japanese scientists noticed something odd about some bacteria they were studying: regularly repeating sequences of DNA whose “biological significance is unknown.” They called them “clustered regularly interspaced short palindromic repeats,” or CRISPR, pronounced like the drawer in your refrigerator where you leave your produce until it wilts. It turned out that they were actually part of the bacteria’s immune system. “Whenever the bacteria’s enzymes manage to kill off an invading virus, other little enzymes will come along, scoop up the remains of the virus’s genetic code, cut it up into little bits, and then store it in those CRISPR spaces.” And then the bacteria use the genetic information they have stored like a mug shot, matching up the RNA in any new virus to see if it, too, needs to be chopped up and stored away.3 Anyway, at a certain point just a few years ago, some scientists recognized that the talent of this enzyme, called Cas9, could be put to good use. If they fed it artificial RNA—a fake mug shot, as it were—it would search for anything with that same code and start cutting.

  Which scientist figured it out and exactly when is a matter of some dispute, with billions of dollars riding on the outcome. In 2012, Jennifer Doudna at Berkeley and a Swedish researcher named Emmanuelle Charpentier published a paper showing that they could use the technique to slice any genome at any place they desired. The next year, Feng Zhang, at Boston’s Broad Institute, demonstrated that it worked with human and mouse cells; and Harvard’s George Church showed a slightly different technique that worked on human cells. What’s not in dispute is that CRISPR provides genetics researchers with something resembling that “word processor” they’d always hoped for. “Gene editing went from being laborious and expensive to simple and cheap,” Vox reported in December 2017. “In the past, it might have cost thousands of dollars and weeks or months of fiddling to alter a gene. Now it might cost just $75 and only take a few hours. And this technique has worked on every organism it’s been tried on.”4 As Doudna herself put it, “The genome—an organism’s entire DNA content, including all its genes—has become almost as editable as a simple piece of text.… Practically overnight, we have found ourselves on the cusp of a new age in genetic engineering and biological mastery.”5

  In the first flush of power, as Doudna describes in her book A Crack in Creation, biologists created genetically enhanced beagles with “Schwarzenegger-like supermuscular physiques” by making “single-letter DNA changes to a gene that controls muscle formation.” By inactivating a single pig gene, researchers have “created micropigs, swine no bigger than large cats, which can be sold as pets.”6 It doesn’t work perfectly yet—stock prices for some genetics firms dropped sharply in the summer of 2018 after researchers found that some “human cells resist gene editing by turning on defenses against cancer, ceasing reproduction, and sometimes dying”7—but experts called this setback a bump in the road, and were busily plotting the next advances: a new revolution in crop genetics, for instance, that will raise again the questions of whether genetically modified food is safe to eat (almost certainly yes) and whether it upends traditional agriculture (almost certainly yes). And they’re exploring unleashing the power of “gene drives,” where scientists can force new traits into wild populations of, say, mosquitoes at “unprecedented speeds, a kind of unstoppable, cascading chain reaction.”8 But we’re not going to talk about those, because this particular book is about our species. For our game, the real power of CRISPR comes with the ability to change people.

  This power comes in two forms, and the distinction between them is key. The first use of this power is to fix existing humans with existing problems. The second would be to alter future humans. They are very different, and we will need to think hard about them, because one improves the human game, and the other might well end it.

  Let’s begin with the first type, the benign one. Scientists refer to it as “somatic genetic engineering,” but another name would be “gene therapy.” Or you could just call it “repair.” In laboratory-grown human cells, CRISPR has already been used to “correct the mutations responsible for cystic fibrosis, sickle cell disease, and some forms of blindness,” Doudna reports. “Researchers have corrected the DNA mistakes that cause Duchenne muscular dystrophy by snipping out only the damaged region of the mutated gene, leaving the rest intact.”9 Say someone has sickle-cell anemia. It now seems entirely possible to isolate stem cells from a patient’s bone marrow, use CRISPR to repair the cells’ mutated genes, and then return the edited cells to the patient, where they will “churn out robust amounts of healthy hemoglobin.”10 This kind of work has just begun to leave the laboratory and enter the real world. In the summer of 2017, the FDA approved the first-ever such treatment, this one designed to modify a patient’s own cells to fight leukemia. The drug company Novartis had altered the cells of sixty-three patients, and fifty-two of them went into remission—a legitimate miracle. “We believe that when this treatment is approved it will save thousands of lives around the world,” the father of a girl named Emily Whitehead told the FDA panel. When Emily was six, she had very nearly died, but then altered genes left her body cancer-free. “I hope that someday all of you on the advisory committee can tell your families that you were part of the process that ended the use of toxic treatments like chemotherapy and radiation as standard treatments, and turned blood cancers into a treatable disease that most people survive,” said Emily’s dad.11

  So, again, let’s be clear: this first kind of genetic engineering, the repair of defects in existing human beings, does not present a threat to the human game. Somatic engineering extends traditional medicine, allowing us to cure some diseases we were unable to treat before, or that we could attack only crudely, with massive doses of chemicals or radiation. Yes, there are all the usual complications that come with Big Pharma’s profit motives and with our unequal health care system. But this kind of work is going to happen, and it is going to make lives better. Three cheers for Kurzweil’s law of accelerating information returns, which made it possible.

  Or, maybe, two cheers. Because CRISPR, as I’ve said, also allows for a second type of power. In this second case, we could change humans before they are born, altering their DNA in embryo; in this case, the changes would be passed on forever to their offspring.

  The first category, as I’ve said, is called somatic genetic engineering; this second approach usually travels under the name of “germline” genetic engineering, because the germ line consists of those cells that pass on their traits in the course of reproduction. You could also call it heritable genetic modification. “Now, for the first time ever,” says Doudna, we possess the power to “direct the evolution of our own species. This is unprecedented in the history of life on earth. It is beyond our comprehension.”12

  Ever since Watson and Crick discovered the double helix, ethicists have debated the possibility of designing babies, but it’s always been a somewhat remote and academic debate, because no one thought it could actually be done anytime soon. Then, CRISPR. In April 2015, researchers at Sun Yat-Sen University, in Taiwan, announced that they had used the technique to edit the genomes of nonviable human embryos, modifying the gene that produces thalassemia, a blood disorder. In 2017 a team in Oregon repeated the feat, th
is time focusing on a genetic defect that produces heart disease; their lab was more successful in its technique, with fewer “off-target effects,” and the researcher who did the work said he hoped to commercialize the process soon. “I have a very strong opinion on clinical applications. This research was not done to satisfy my curiosity,” the Oregon researcher said. “This was done to develop the technology and bring it to clinics. It may take a decade, but we will be there.”13

  In the event, it took considerably less than a decade. In late November 2018, another Chinese researcher, He Jiankui, announced that a newborn pair of twin girls, Lulu and Nana, had been genetically altered in his lab before their birth, making them Earth’s first designer babies. The story was bizarre: he’d reprogrammed their genes in an effort to make sure that they wouldn’t be able to contract the HIV infection, even though, as the AIDS researcher Anthony Fauci quickly pointed out, “there are so many ways to adequately, efficiently, and definitively protect yourself against HIV that the thought of editing the genes of an embryo to get to an effect that you could easily do in so many other ways in my mind is unethical.” Apparently the “fix” only took with one of the newborns; there was speculation that the other might have been damaged in the process.14 Dr. He had already crossed lines: most government and scientific societies have some form of law or regulation against germline engineering, and the Chinese authorities announced that they were suspending his clinical trial; indeed, there was speculation that he may have been arrested, after a government spokesman called his experiment “extremely abominable.”15

  But clearly the lines are weakening. Doudna said in 2017 that she thought CRISPR shouldn’t be used to edit embryos “today, but in the future possibly. That’s a big change for me.” She had shifted her thinking, she said, after reading letters from people with genetic disease in their family. She’d received one just the other day, from a mother with a son diagnosed with a neurodegenerative disease. “He was this adorable little baby, he was in his little carrier and so cute,” she recalled. “I have a son and my heart just broke.… And you think, if there were a way to help these people, we should do it. It would be wrong not to.”16

  Which is true—one of the better traits of human beings is our general inability to ignore cute babies in distress. (And all babies are cute.) But it’s also true (and this is almost the last technical paragraph) that we already have a way, in widespread use, to prevent genetic disease of precisely this type. It’s called preimplantation genetic diagnosis (PGD), and here’s how it works: Parents at risk for genetic disease use in vitro fertilization to produce a number of embryos—say, eight of them. A lab grows the embryos for five or six days, to the point where they can be tested to see if they carry the problem genes. The doctor then selects an embryo that’s free from the disease and implants it in the mother’s womb, and on we go. This has been done millions of times around the world. All the diseases, such as thalassemia, that researchers have shown can be eradicated with germline engineering are already routinely selected against with PGD.

  In both cases, the eggs are taken out of the mother and their material manipulated on the laboratory bench; for the mother, the procedures are equally invasive. But PGD is not particularly controversial for a simple reason: You are working with the genetic material provided by the parents. You’re not adding something new; you’re just eliminating the dangerous possibilities presented by the mathematics of genetics. The only, vanishingly rare, cases where it doesn’t work are when both parents suffer from the same recessive genetic disorder. If both parents actually have cystic fibrosis, every single child they conceived would carry the disease as well—there would be no healthy eggs from which to select. But those cases are, indeed, vanishingly rare—these are the people who, absent germline engineering, would have to adopt children or use eggs or sperm from someone else.

  PGD works so routinely that journalists routinely ignore it. One study from the Center for Genetics and Society found that 85 percent of articles on human genetic engineering don’t even bother to mention that an obvious alternative already exists. In fact, PGD works so well that there are worries it could be misused. Doubtless some people are already selecting the sex of their child, which in a sexist world should worry us. But even those worries pale when compared to genetic engineering, because of the natural limits imposed by the parents’ existing genes. PGD allows you six or eight possible people, but they are all within the realm of existing chance.

  What makes germline engineering attractive to some is precisely that it offers the chance to go beyond those limits, to achieve results that nature acting alone could not produce. Instead of selecting from existing possibilities, it will allow us to add new choices to the menu. Dr. He’s alteration that aimed at preventing future HIV infection was the barest start. Let Paul Knoepfler, professor in the Department of Cell Biology at the University of California, Davis, School of Medicine, explain what lies ahead: “In the same way that today you might order a customized pizza with green olives, hold the onions, Italian ham, goat cheese and a particular sauce, when you design and order your future GMO sapiens baby you could ask for very specific ‘toppings,’” he says. “In this case, toppings would be your choice of unique traits, selected from a menu: green eyes, hold the diseases, Italian person’s gene for lean muscle, fixed lactose intolerance, and a certain blood type.”17

  As we gain a better understanding of how the human genome works, as we get more computer power and understand better the interactions among various genes, the menu will naturally get longer and more startling. Listen, for instance, to Dean Hamer, the former chief of gene structure and regulation at the National Cancer Institute’s Laboratory of Biochemistry, describe a scene in the near future, when a young couple—he called them Syd and Kayla—get together to tweak their fetus: “They pondered the choices before them, which ranged from the altruism level of Mother Teresa to the most cutthroat CEO. Typically, Syd was leaning toward sainthood; Kayla argued for an entrepreneur. In the end, they chose a level midway between, hoping for the perfect mix of benevolence and competitive edge.” Syd and Kayla were also careful not “to set their child’s happiness rheostat too high. They wanted her to be able to feel real emotions. If there was a death[,] they wanted her to mourn the loss. If there was a birth, she should rejoice.”18 As the veteran University of Alabama professor Gregory Pence, a pioneer in the field of bioethics, once put it, “Many people love their retrievers and their sunny dispositions around children and adults. Would it be so terrible to allow parents to at least aim for a certain type, in the same way that great breeders … try to match a breed of dog to the needs of a family?”19

  Pence and Hamer were writing in the late 1990s—I quoted them first in a much earlier book called Enough. In those days all this was still speculative: genetic alteration was too difficult for it to be a commercial possibility, and we still had a very limited sense of which genes control mood, intelligence, disposition. Since then, we’ve learned considerably more, to the point where those early predictions sound a little simple-minded. Now we think more in terms of how genes interact. In the summer of 2018, new studies of the genetics of twenty thousand patients on three continents showed that you could track a person’s “polygenic score,” measuring information “from across someone’s genes to assess their influence on educational success, career advancement, and wealth.” Find two kids from the same parents growing up in the same home—“the one with the higher polygenic score tends to go farther,” which is to say, gets richer.20 So, it’s not hard to imagine how Big Data and Big Biotech will eventually combine, as Kurzweil insists, to produce a (big) new industry.

  There’s plenty we still don’t know, of course. The day after the news broke about the CRISPR-altered embryos in the Oregon lab, a New York Times reporter declared that science was “unlikely” to “genetically predestine a child’s Ivy League acceptance letter, front-load a kid with Stephen Colbert’s one-liners, or bake Beyoncé’s vocal range into a baby,”
because none of these abilities was located on a single gene.21 As a Stanford professor explained, we aren’t able to examine a stack of embryos and say, “this one looks like a 1550 on the two-part SAT.”22 There are, thankfully, an awful lot of genes involved in making someone smart or sassy.

  However, we know a lot more than we used to about which genes regulate, say, the levels of serotonin in our bodies; it’s not at all far-fetched to imagine scientists trying to produce some changes in a child’s temperament. “This is a pivotal point in the push toward genetically modified humans,” said Marcy Darnovsky, the head of the Center for Genetics and Society, the day after the Oregon announcement. “A small group of scientists have taken it upon themselves to move forward with reproductive germline modification technologies. Allowing any form of human germline modification leaves the way open for all kinds—especially when fertility clinics start offering ‘genetic upgrades’ to those able to afford them.”23

  In fact, given that PGD already lets you deal with disease, CRISPR may well end up being less about saving cute babies from genetic illness and more about “improvement.” Jennifer Doudna tells a startling story: Not long after news emerged of her CRISPR breakthrough, one of the PhD students in her lab, Sam Sternberg, got an email “from an entrepreneur I’ll call Christina. She wanted to know if Sam would be interested in being part of her new company, which somehow involved CRISPR, and she asked him to meet so she could pitch her business idea.” When Sam and Christina sat down “at an upscale Mexican restaurant near campus,” she began “speaking passionately over cocktails” about how she hoped her business would offer “some lucky couple the first healthy ‘CRISPR baby,’” with “customized DNA mutations, installed via CRISPR, to eliminate any possibility of genetic disease.” As she tried to lure him aboard, she stressed that she wanted him to work only on diseases, but he was so rattled that he “excused himself before dessert.” He’d perceived a “Promethean glint in her eyes and suspected she had in mind other, bolder genetic enhancements.”24