She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity (70 page)

TERT was just one candidate among many that Church saw for enhancement. Editing genes to treat wasting muscles might lead to people enhancing their strength. Researchers are discovering ways to fight the decline in memory and learning that comes with Alzheimer's. Gene therapy could conceivably deliver the same results. And editing those genes in healthy people might enhance their cognition. Parents might choose to edit those same genes in their children to give them an edge in school and at work.

“I think enhancement will creep in the door,” Church told the audience.

In one sense, Doudna's campaign was a success. She had succeeded in getting a conversation started. By 2016, CRISPR had cracked open its cocoon and was a full-blown media butterfly, the subject of regular coverage on television and in the newspapers. Doudna hopped from city to city to explain the awesome tools she had helped invent and to provoke discussions about its use.

That conversation's center of gravity soon shifted in a profound way. The National Academy of Sciences brought together
a committee of twenty-two experts—including biologists, bioethicists, and social scientists—to grapple with the science, ethics, and governance of human genome editing. In February 2017, they released a 260-page report on their deliberations. Instead of kicking the germ line editing can even farther down the road, they came to a startling agreement. They endorsed clinical trials for treating serious diseases for which there were no other alternative treatments.

In their report, the committee asked readers to consider the case of Huntington's disease. Karen Mulchinock was able to prevent her children from inheriting the disease by using preimplantation genetic diagnosis. Because she carried only one defective copy of the HTT gene, she could pick out embryos that inherited her good copy. If two people with Huntington's have children, however, their children run a 25 percent risk of inheriting the disease-causing copy of the gene from both parents. In these rare cases, preimplantation genetic diagnosis offers no help. Genome editing might. “The number of people in situations like those outlined above might be small, but the concerns of people facing these difficult choices are real,” the committee observed.

Shortly after the genome editing committee released their report, Shoukhrat Mitalipov published an experiment that suggested that
these clinical trials could very well succeed. Mitalipov followed Junjiu Huang's example and tried to erase a genetic disorder by editing human embryos. Unlike Huang, however, Mitalipov and his colleagues manipulated viable embryos rather than doomed ones. They did everything they could to keep
the embryos viable. And while Huang's team used relatively crude CRISPR tools, Mitalipov took advantage of newer, more precise ones.

For their experiment, Mitalipov chose a genetic disease of the heart known as hypertrophic cardiomyopathy. Mutations to a gene called MYBPC3 cause the heart's walls to thicken and falter. Without warning, people with the disease may die of a sudden heart attack. The disorder is dominant, meaning that a child need inherit only one copy of the faulty gene to develop a faulty heart.

Mitalipov's team got sperm from a man suffering from hypertrophic cardiomyopathy and used it to fertilize healthy eggs. They also delivered CRISPR molecules tailored to seek out the mutation on the MYBPC3 gene. Out of fifty-four embryos treated this way, thirty-six ended up with two healthy copies of the gene. Another thirteen ended up as mosaics.

By the time Mitalipov's CRISPR molecules made their way inside the fertilized eggs, they had already made a new copy of their DNA. The CRISPR molecules apparently edited only one copy, so that when the embryo divided into two cells, one had the defective MYBPC3 gene and the other didn't. As the embryo continued to grow, new cells inherited one version of the gene or the other.

To avoid making mosaics, Mitalipov's team tried a new method. They edited the mutation-carrying sperm, and then used them to fertilize eggs. In these trials, 72 percent of the embryos lost the mutation. Mitalipov and his colleagues found that their edited embryos developed normally for eight days. If they had implanted those embryos instead in a woman's uterus, they might well have developed into babies with healthy hearts.

I was on vacation with my family in a little English village in August 2017 when the news broke of Mitalipov's experiment. I had hoped to take a break from CRISPR, filling my days with footpath walks and visits to castles. But one day I walked into the local grocery store and spotted a newspaper with four-cell human embryos scattered across its front page.

“
The Cells That Could End Genetic Disease,” it blared. That evening, I turned on the television at our cottage, only to encounter Mitalipov talking about his experiment. CRISPR was becoming inescapable.

For all the attention the world gave Mitalipov's research, he didn't promise much from it. Parents who carry variants for hypertrophic cardiomyopathy can already use preimplantation genetic diagnosis to identify embryos that won't develop the disease. CRISPR might help them deal with simple Mendelian inheritance, which leaves them with only 50 percent of their embryos to implant, lowering the odds of a successful birth.

“Gene correction would rescue mutant embryos, increase the number of embryos available for transfer and ultimately improve pregnancy rates,” Mitalipov and his colleagues wrote in their paper.

By narrowing his focus, Mitalipov made the ethical challenges of CRISPR seem manageable. He just wanted to improve the odds that parents could have healthy families. Likewise, other scientists who contemplated germ line engineering with CRISPR simply wanted to cure hereditary diseases in the womb, rather than wait to treat somatic cells later in life.

Within this narrow focus, a lot of the ethical concerns that have been raised about CRISPR seem less like dystopian nightmares than the everyday challenges that conventional medicine already poses. If CRISPR turns out to work reliably, we might well face a world where hereditary diseases are a bigger burden on those who can't afford it. But the cost of medicine has been a grave problem for generations, and many recent advances have made this inequality more dire. As gene therapy has inched its way to the clinic, companies have begun floating astonishing price tags for the treatment. A single shot of gene-carrying viruses might cost a million dollars or more. Yet no one has responded to this figure by demanding that gene therapy be banned. There's nothing wrong with gene therapy in itself, only with the ability of some people to get it while many others can't. That's a problem of politics, of economics, of regulations. If we are worried some people can't get CRISPR, then the solution is obvious: CRISPR for everyone.

The question of consent isn't new to germ line engineering either. We don't require that children give their consent in order to get vaccines or
antibiotics. That's what parents are for. If conventional medicine fails to help sick children, their parents may give their consent to experimental treatments, knowing full well their children may not be cured and may even suffer as a result. Early in the history of gene therapy research, parents started enrolling their children in studies. It was a profound decision for the parents to make, weighing the grave diseases their children suffered against the possibility that some side effect would emerge. It was especially serious for gene therapy studies, since the children would be carrying genes in their cells possibly for the rest of their lives. Yet no one has responded to these difficult ethical choices by calling for all gene therapy to be banned.

As for the ethics of enhancements, we already live in a world in which parents try to enhance their own children's prospects. And many of those enhancements are already spread out unfairly. In 2010,
American parents whose income was in the top 10 percent spent more than $7,000 on young children, including books, computers, and musical instruments. Parents in the bottom 10 percent spent less than $1,000.

In some cases, societies have managed to spread enhancements beyond the wealthy few. Vaccinations enhance our immune systems by priming them to fight measles and other diseases. The world has committed itself to getting as many children vaccinated as possible. That's a noble achievement. But, as a society, we still fall shamefully short in other respects.

While some enhancements should be spread more fairly, other enhancements are simply misguided. Some parents insist on having their short children treated with human growth hormone—not because they're sick, but because their parents want to give them social advantages that come with being tall. This push for enhancement can lead instead to insecurity, as children feel inadequate in their parents' eyes, despite being perfectly healthy.

If we treated embryo editing in this way—as very early gene therapy—we would probably muddle our way to a new normal. We'd allow it much as we allow in vitro fertilization. We'd debate whether this or that use of CRISPR is acceptable. We'd ban some, approve others. Altering some genes
might turn out to have dangerous side effects, and regulations would need to be put in place to keep children safe. Somebody would certainly sneak off and try a reckless treatment, and we'd try to make sure no one ever did so again. And, in time, CRISPR would become a responsible form of medicine.

But editing embryos is not merely another form of medicine. As David Baltimore made plain at the outset of the international meeting in 2015, what made it so unsettling was the possibility that we could use CRISPR to alter the future of human heredity. We were climbing into the chariot of the sun without knowing if we were wise enough to control its course.

It's heredity that matters most, and yet we have given surprisingly little reflection about why it matters so much, or how our actions would actually alter it.

One of the few people to think through the ethics of altering heredity was
a theologian named Emmanuel Agius. In 1990, years before CRISPR even had a name, Agius argued that germ line editing would rob future generations of their inheritance.

“The collective human gene pool knows no national or temporal boundary, but is the biological heritage of the entire human species,” Agius said. “No generation has therefore an exclusive right of using germ line therapy to alter the genetic constitution of the human species.”

But what would it really mean to alter the genetic constitution of a new species? People have sketched out many scenarios: a utopia without disease; a dystopia where the rich enjoy genetically enhanced intelligence and health while the poor endure nature's miseries. Some have even claimed that we will turn
Homo sapiens
into a new species altogether.

These are dreams. Sometimes dreams prove prophetic. Sometimes they prove to be fantasies. Hermann Muller's dream of Germinal Choice got some parts of the future right, and some parts wrong. He assumed a socialist government would protect the future of the human gene pool. He may well have been shocked if he had lived long enough to see sperm banks, in
vitro fertilization, and preimplantation genetic diagnosis take hold thanks to capitalism instead. Parents did not volunteer for duty as he envisioned. They became consumers.

Whichever future we end up in, the path will have to start from where we are today. Preimplantation genetic diagnosis might be the beginning of a major shift in how children are born. In 2014—thirty-six years after the first test-tube baby was born—only 65,175 babies in the United States were born from in vitro fertilization. That's about 1.6 percent of the American babies born that year. Of those, only a small fraction went through preimplantation genetic diagnosis (it's hard to get precise numbers). Worldwide, there might be tens of thousands of children who went through it. Together, they make up only a hair-thin fraction of the 130 million babies born each year worldwide. But with each year, more parents are choosing the procedure—in some cases, encouraged by their governments. In a 2010 study, researchers investigated how much money would be saved if a couple used preimplantation genetic diagnosis to avoid having a child with cystic fibrosis. A $57,500 procedure
could avoid $2.3 million in medical costs over a lifetime.

Today, parents typically use preimplantation genetic diagnosis if they already know their children are at risk of particular diseases. As DNA sequencing speeds up, it will become possible for doctors to scan every gene in an embryo, detecting hereditary diseases that parents may not know they carry. It would be a seductive offer. I can imagine how it would work by looking at my own genome. It turns out, for example, that one of my copies of a gene called PIGU has a mutation that puts people at greater risk of skin cancer. If I had my druthers, I'd prefer my children to inherit my good copy and not my bad one. Either way, they'd still be inheriting my DNA.

And it would be hard to stop there. I have also discovered I have a variant of a gene called IL23R that dramatically
lowers
my risk of certain disorders. Those disorders include Crohn's disease, a chronic inflammation of the gut, and ankylosing spondylitis, which fuses the vertebrae in the spine, causing chronic pain and forcing people to hunch forward. What they have in common is the immune system going haywire and attacking the body's own tissue. No one knows exactly what triggers this attack, but it appears
my variant of IL23R—found in only 8 percent of people with European ancestry—tamps down the immune system's communication network. My variant is so potent, it turns out, that drugmakers used its biology as the basis for drugs for autoimmune disorders. As a parent, I would do anything I could to lower the risk that my children get diseases that put their back into howling pain or that give them a lifetime of intestinal distress. To give my children my protective copy of IL23R, rather than the ordinary one, would be the least I could do.

If governments allowed it, some parents might ask if they could pick out their variants that could influence other traits in their children. Preimplantation genetic diagnosis on its own would usually fail to produce big results. But there might be exceptions. Scientists have found a mutation on a gene called STC2 that alters a hormone our bodies make, called stanniocalcin. One copy of the mutant version can make a person three-quarters of an inch taller. But only one in a thousand people carry it.