The Code Breaker, page 31
David Sanchez
CHAPTER 41 Thought Experiments
Huntington’s disease
Before our knees jerk and we stumble into hard-and-fast pronouncements—Somatic editing is fine but inheritable germline edits are bad; Treatments are fine but enhancements are bad—let’s explore some specific cases and see what questions they raise.
If ever there was a case for editing a human gene, it would be for getting rid of the mutation that produces the cruel and painful killer known as Huntington’s disease. Caused by an abnormal repetition of letters in a DNA sequence, it eventually leads to the death of brain cells. Beginning in middle age, victims start to twitch uncontrollably. They cannot focus. They lose their jobs. Eventually they are unable to walk, then talk, then swallow. Sometimes dementia sets in. It is an agonizing death in very slow motion. And it is devastating for the families—especially the kids, who watch their parent’s gruesome decline, face the pity or ridicule of their schoolmates, and eventually learn that they have at least a 50 percent chance of suffering the same fate. One must be a fanatic believer in salvation through suffering to think that any good comes from its existence.1
Huntington’s is a rare dominant disease; even one copy of the mutation spells doom. Symptoms usually arise only after a person’s childbearing years, so its victims often have children before they know they have the genetic disease. Therefore, it’s not weeded out by natural selection. The evolutionary process cares little about what happens to us after we have children and get them to a safe age, so there are a whole bunch of middle-aged maladies, including Huntington’s and most forms of cancer, that we humans would want to eliminate, even though nature sees no need to.
Fixing Huntington’s is not a complex edit. The wild sequence of excess DNA serves no good purpose. So why not edit it out in the germline of afflicted families—and out of our species once and for all?
One argument is that it would be better, where possible, to find an alternative approach to germline gene editing. In most cases—except when both parents have the disease—it might be possible to assure healthy children through preimplantation genetic diagnosis. If the parents can produce enough fertilized eggs, the ones with Huntington’s can be weeded out. But producing a lot of viable eggs, as anyone who has been through fertility treatments knows, isn’t always easy.
Another alternative is adoption. That, likewise, is not always easy these days. In addition, prospective parents often want to have a genetically related child. Is that a reasonable desire or just vanity?2 Whatever some ethicists may say, most parents would feel it is reasonable. Millions of years of struggle by organisms, from bacteria to humans, to find ways to pass on their genes show that the impulse to produce genetically related offspring is among the most natural on this planet.
In making a gene edit to eliminate Huntington’s, nothing has been altered except the elimination of the horrific mutation. So should it be permissible to do so, especially in cases where preimplantation screening is difficult? Even if we decide to set a high bar for the use of germline editing, it seems (at least to me) that Huntington’s is a genetic malady we should try to eliminate from the human race.
If so, what other genetic problems should parents have the right to prevent from being passed along to their babies? Because this slope is slippery, let’s take it step by step.
Sickle cell
Sickle-cell anemia is an interesting next case to consider because it raises two complexities, one medical and the other moral. Like Huntington’s, sickle cell is caused by a simple mutation. In people who inherit a bad copy of the gene from both parents, the mutation distorts red blood cells, which deliver oxygen to the tissues of the body, into the shape of a sickle. Because these sickled cells die more quickly and have a harder time moving through the body, the disease can lead to fatigue, infections, spasms of pain, and early death. It tends to strike Africans and African Americans.
By 2020, trials were underway for somatic sickle-cell therapies, including the one described earlier involving the Mississippi woman Victoria Gray, who was part of a clinical trial in Nashville. Blood stem cells are removed from patients, edited, and then reinserted into the body. But this is an extraordinarily expensive procedure, not feasible for the more than four million afflicted globally. If the sickle-cell mutation could be fixed in the germline, by editing eggs or sperm or early-stage embryos, that would be a cheaper, one-time cure that would be inherited and could eventually eliminate the disease from our species.
So, does it fall into the same category as Huntington’s? Is it a disease that should be eliminated using inheritable edits?
Well, as with many such genes, there’s a complexity. People who get a copy of the gene from only one parent do not develop the disease, but they do develop immunity to most forms of malaria. In other words, the gene was (and in some places still is) useful, especially in sub-Saharan Africa. Now that there are treatments for malaria, it’s less useful. But it is a reminder, when we think of messing with Mother Nature, that genes may play multiple roles and have evolutionary reasons for existing.
Let’s suppose that researchers show that editing out the sickle-cell mutation is safe. Would there then be any reason to prohibit patients from having the gene edited out when they conceive children?
At this point in the discussion, a delightful kid named David Sanchez pops up to add another bit of complexity. He’s a plucky, charming, reflective, African American teenager in California who loves to play basketball, except when his sickle-cell anemia causes him to double over in pain. At one point he developed a chest syndrome when the sickled cells blocked the blood to his lungs, and he had to drop out of high school. In a powerful 2019 documentary about CRISPR, Human Nature, he is an unlikely star. “My blood just does not like me very much, I guess,” he says. “Sometimes you have a little sickle-cell crisis. Sometimes you have a really bad one. But I’m not just going to not play basketball.”3
Every month, Sanchez’s grandmother takes him to Stanford University Children’s Hospital, where he gets an infusion of healthy cells from a blood donor. That gives him temporary relief. Matthew Porteus, the gene-editing pioneer at Stanford, has been helping to treat him. At one point he explained to Sanchez that, someday in the future, germline gene editing might eliminate the disease. “Maybe one day with CRISPR,” Porteus told him, “they could go in and change the gene in the embryo so that the kid, when it’s born, doesn’t have sickle cell.”
Sanchez’s eyes lit up. “I guess that’s kind of cool,” he said. Then he paused. “But I think that should be up to the kid later.” Asked why, he reflected for a moment and then continued slowly. “There’s a lot of things that I learned having sickle cell. Because I had it, I learned patience with everyone. I learned how just to be positive.”
But would he like to have been born without sickle cell? Again, he pauses. “No, I don’t wish that I’d never had it,” he says. “I don’t think that I would be me if I didn’t have sickle cell.” Then he bursts into a big and lovely smile. He was born to be in such a documentary.
Not everyone with sickle cell is like David Sanchez. Even David Sanchez may not always be like the David Sanchez in the documentary. Despite what he said on camera, it is hard for me to imagine a kid choosing to have sickle cell rather than not having it. It’s even more difficult to imagine parents, especially ones who have themselves endured a life with sickle cell, deciding that they want their kids to have it. After all, Sanchez is enrolled in a program to keep his sickle-cell anemia at bay.
The question gnaws at me, so I arrange to pose some questions to Sanchez.4 This time his thinking is a bit different than when he was interviewed for the documentary. On complex personal issues like this, our thoughts understandably tend to fluctuate. Would you like to find a way, I ask him, to make sure your children are born without sickle cell? “Yes,” he responds. “If that’s an option, then of course.”
What about the patience and the positive attitude that, as he told the documentary producers, he learned by having sickle cell? “Empathy is something that’s really important to humans,” he responds. “That is something I learned from sickle cell, and that is something I would really want to convey to my kids if they could be born without sickle cell. But I wouldn’t want my kids or others to go through what I went through.” The more he learns about CRISPR, the more excited he becomes about how it may cure him and protect his children. But it’s complicated.
Character
David Sanchez’s wise words bring up a larger question. Challenges and so-called disabilities often build character, teach acceptance, and instill resilience. They may even be correlated to creativity. Take Miles Davis. The pain of sickle cell drove him to drugs and drink. It may have even driven him to his death. It also, however, may have driven him to be the creative artist who could produce Kind of Blue and Bitches Brew. Would Miles Davis have been Miles Davis without sickle cell?
This is not a new question. Franklin Roosevelt was forged by polio. The challenge transformed his character. Likewise, I knew a guy who was one of the last kids to be touched by polio before Salk and Sabin came up with their vaccines in the late 1950s. He achieved success, I think, partly because of his great depth of character, and he taught all of us about grit and gratitude and humility. My favorite novel, Walker Percy’s The Moviegoer, tells of the transformative effect the disabled boy Lonnie has on the other characters.
The bioethicist Rosemarie Garland-Thomson, who was born with distorted arms, tells of the friendship circle she has with three other women born with genetic conditions, one blind, one deaf, and one with muscular impairment. “Our genetic conditions gave us a head start in accessing multiple opportunities for expression, creativity, resourcefulness, and relationships—for human flourishing,” she writes.5 Similarly, Jory Fleming is an amazing young man who was born with severe autism as well as other challenging health conditions. He could not cope in class, so he was homeschooled. As he grew older, he taught himself how to deal with the fact that his internal world was different from those of other people. He ended up winning a Rhodes Scholarship to Oxford. In his 2021 memoir, How to Be Human, he reflects on whether gene editing should be used, if it becomes feasible, to eliminate some of the causes of autism. “You’d be removing an aspect of the human experience,” he writes, “but for what benefit exactly?” Autism, he argues, is a difficult condition to have, but the challenges largely come because the world is not good at accommodating people whose emotional lives are different. Those differences can actually provide a useful perspective for the rest of us, including on how to make decisions that are not unduly influenced by emotion. “Should society change to recognize the benefits of autism instead of just the challenges?” he asks. “Certainly, my experience has been very challenging, and it has been also rewarding. And who knows, hopefully, I’ll be able to do something with my life that benefits other people in some way.”6
It’s an interesting dilemma. Once a vaccine was discovered to stop polio, we humans quickly and easily decided to use it to eliminate that disease from our species, even at the risk of allowing future Franklin Roosevelts to remain unforged. Using gene editing to prevent disabilities may make society less diverse and creative. But does this give governments the right to tell parents they can’t use such technologies?
Deafness
That raises the question of what attributes should be labeled disabilities. Sharon Duchesneau and Candy McCullough are a lesbian couple who wanted a sperm donor so they could conceive a kid. Both of them are deaf. They consider their deafness to be part of who they are rather than something to be cured, and they wanted a child who would be part of their cultural identity. So they advertised for a sperm donor who was congenitally deaf. They found one, and now they have a deaf child.
A story about the couple in the Washington Post caused them to be condemned by some people for inflicting a disability on a child.7 But they were applauded in the deaf community. Which was the right response? Should they be criticized for making sure their child had a disability, or should they be praised for preserving a subculture that contributes to the diversity and perhaps even the empathy of society? Would it be different if, instead of using a deaf sperm donor, the couple had used preimplantation diagnosis to select an embryo that had the genetic mutation for deafness? What if the embryo was typical, but they edited it to be deaf? Would that be okay? What if they asked a doctor to punch out the child’s eardrums after birth?
In some cases when formulating a moral argument, it helps to do a reversal test. The Harvard philosopher Michael Sandel uses this thought experiment: Suppose a parent comes to a doctor and says, “My child is going to be born deaf, but I want you to do something to make her able to hear.” The doctor should try, right? But now suppose a parent says, “My child is going to be born able to hear, but I want you to do something to her to make sure she is born deaf.” I think most of us would recoil if the doctor agreed. Our natural instinct is to consider deafness a disability.
How do we distinguish between traits that are true disabilities and ones that are disabilities mainly because society is not good at adapting for them? Take the case of the deaf lesbian couple, for example. Some people may consider both the fact that they are deaf and the fact that they are lesbian as disadvantages. What if they wanted a genetic procedure that would make their child more likely to be straight? Suppose they chose the reverse and wanted to make it more likely their child would be gay? (This is a thought experiment. There is no simple gay gene.) Likewise, being born Black in America could be considered a disadvantage. A single gene, SLC24A5, has a major influence on determining skin color. What if a set of Black parents considers their race to be a social handicap and wants to edit that gene to produce light-skinned babies?
Such questions prompt us to look at “disabilities” and ask to what extent they are inherently disabling and to what extent the disadvantage is due to our social constructs and prejudices. The disadvantages from being deaf, for a human or any other animal, are very real. In contrast, any disadvantages to being gay or Black are due to social attitudes that can and should be changed. That is why we can make a moral distinction between using genetic techniques to prevent deafness and using these techniques to influence such things as skin color and sexual orientation.
Muscles and sports
Now let’s do some thought experiments to see if we might want to cross the blurry line between gene editing that is done to treat true disabilities and gene editing that is done to enhance the traits of our children. The MSTN gene produces a protein that curtails the growth of muscles when they reach a normal level. Suppressing the gene takes off the brakes. Researchers have already done this to produce “mighty mice” and cattle with “double muscling.” It is what our biohacker Josiah Zayner used to make his kits that produce super-frogs and for the CRISPR he injected into himself.
Among those interested in these types of gene edits, other than cattle breeders, are athletic directors. Pushy parents who want champion children are sure to follow. Especially by using germline editing, they might produce a whole new breed of athletes with bigger bones and stronger muscles.
Add to this mix a rare gene mutation that was discovered in the Olympic champion skier Eero Mäntyranta. Initially accused of doping, he was found to have a gene that increased his number of red blood cells by more than 25 percent, which naturally improved his stamina and ability to use oxygen.
So what do we say to parents who want to use gene editing to produce bigger, more muscular kids with greater stamina? Ones who can run marathons, break tackles, and bend steel with their bare hands? And what does that do to our concept of athletics? Do we go from admiring the diligence of the athlete to admiring instead the wizardry of their genetic engineers? It’s easy to put an asterisk next to the home run tallies of José Canseco or Mark McGwire when they admit that they were on steroids. But what do we do if athletes’ extra muscles come from genes they were born with? And does it matter if those genes were paid for by their parents rather than bestowed by a random natural lottery?
The role of sports, at least since the first Olympics in 776 BC, is to celebrate two things: natural talent combined with disciplined effort. Enhancements would shift that balance, making human effort less of a component of victory. Therefore the achievement becomes a little less praiseworthy and inspiring. There is a whiff of cheating if an athlete succeeds by obtaining some physical advantages through medical engineering.
But there’s a problem with this fairness argument. Most successful athletes have always been people who happened to have better athletic genes than the rest of us. Personal effort is a component, but it helps to be born with the genes for good muscles, blood, coordination, and other innate advantages.
For example, almost every champion runner has what is known as the R allele of the ACTN3 gene. It produces a protein that builds fast-twitch muscle fibers, and it is also associated with improving strength and recovery from muscle injury.8 Someday it may be possible to edit this variation of the ACTN3 gene into the DNA of your kids. Would that be unfair? Is it unfair that some kids are born with it naturally? Why is one more unfair than the other?
Height
One way to think through the fairness of using gene editing for physical enhancements is by looking at height. A condition called IMAGe syndrome, which severely curtails size, is caused by a mutation in the CDKN1C gene. Should it be permissible to genetically edit out this defect so that these kids will grow to an average height? Most of us would think so.
Now let’s take the case of parents who just happen to be short. Should they be permitted to edit the genes of their kids so they will grow to average height? If not, what’s the moral difference between these two cases?
