She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity (71 page)

It's hard to predict how far parents would go as they picked out natural variations. A physicist named Stephen Hsu at Michigan State University has claimed that parents could raise their children's intelligence by selecting from embryos. Their doctors could check for which versions of a hundred genes influencing intelligence each embryo had. The embryo with the highest score could be implanted. Hsu estimated that this selection might, on average, raise a child's IQ score by five to ten points.

Geneticists generally scoff at Hsu's claims. We still know precious little about the genes that influence intelligence. While scientists have zeroed in on some of the genes that likely play a role, it's entirely possible that the true players are nearby genes or gene switches. And since we know so little about how genes for intelligence interact with the environment, picking out certain alleles to give to embryos could wind up having no effect at all.

That skepticism didn't stop Hsu. In 2011, he joined researchers at a Chinese DNA-sequencing center called BGI to found their Cognitive Genomics Lab. They set out to get DNA from two thousand of the world's smartest people and find variants they shared. In 2013, reporters got wind of the project and described it in breathless tones.
“Why Are Some People So Smart? The
Answer Could Spawn a Generation of Superbabies” was the headline of a
Wired
article. “
China Is Engineering Genius Babies,”
Vice
announced.

Vice
claimed that the BGI team was close to finding intelligence alleles and that China had “developed a state-endorsed genetic-engineering project.”
Wired
's John Bohannon suggested that a generation of superbabies might be spawned if a government like Singapore's encouraged parents to use preimplantation genetic diagnosis to pick embryos with high genetic scores for intelligence. Hsu himself found the coverage outrageous. In an interview with the journalist Ed Yong, he simply said, “
That's nuts.”

But Hsu had Muller-size dreams of his own. Imagine that preimplantation genetic diagnosis for intelligence genes became widespread in a country. Now imagine that the children produced from that selection used the procedure on their own children.
In a 2014 essay for
Nautilus
, Hsu argued that this would be no different from what happens when cattle breedings select animals for size or milk yield. With so many variants influencing intelligence, it would be possible to raise intelligence test scores for generations until today's tests would no longer be able to measure it. “Ability of this kind would far exceed the maximum ability among the approximately 100 billion total individuals who have ever lived,” Hsu promised.

In 2017, I e-mailed Hsu to see how his dream was faring. Six years had passed since the Chinese intelligence project had launched. And in that time I had heard of no concrete results. When I contacted Hsu, he told me that BGI had sequenced about half of the two thousand people in the study. Then they got in a business dispute with the company supplying them with their DNA-sequencing equipment.

“As a peripheral consequence,” Hsu said, BGI “cut our project off a few years ago. So, we still to this day have not sequenced all of our samples.”

The first generation of superbabies would have to wait.

Preimplantation genetic diagnosis already allows parents to choose which of their own variants their children can inherit. It may open the door to CRISPR, just as Mitalipov has proposed. If that does happen, it will
not alter heredity any more than we're already altering it by blocking some disease-causing mutations from getting into future generations. At least not at first.

If CRISPR became a standard tool in fertility clinics, people might lose their suspicions of it—just as people lost their suspicions of in vitro fertilization in the 1980s. Before long, people might be willing to entertain a new use for CRISPR. Doctors might edit beneficial changes into an embryo's genes. They might protect children from Crohn's disease by rewriting the IL23R gene. There are other rare variants that show signs of protecting people from Alzheimer's disease, various kinds of cancer, and infectious diseases like tuberculosis.

None of these variants are artificial, since they were discovered in people's DNA. Parents could give their children all the advantages that scientists have found in our species' genetic variations. But more variants keep coming to light with more research. If this practice became popular enough, the Australian philosopher Robert Sparrow has speculated, parents might hold off having children, in the same way people wait to buy a phone until a new model is released. Sparrow wonders if future generations might find themselves stuck in an “
enhanced rat race.”

The choices that parents make about editing embryos would not just affect their children. The alterations could be inherited by their grandchildren. For parents with Huntington's disease, it would probably be a great relief to know their descendants wouldn't be tormented by a faulty HTT gene—unless, of course, they inherited it from another ancestor.

But when we try to look far forward, over the course of many generations, heredity doesn't necessarily work the way we imagine it to. Introducing a single edited gene into the human gene pool does not guarantee that it will take over the human species as Agius promised. In fact, the science of population genetics has found that it's far more likely for a new variant to eventually disappear. Bequeathing an Alzheimer's-fighting variant to your children may seem like a wonderful gift, but it's not a gift that can be reliably passed down through the generations. Imagine your daughter, equipped with two copies of the variant, marries a man who lacks them. Their
children will inherit only one copy apiece. When they have children with people who don't have a copy, many of your great-grandchildren will probably not have any protection left at all.

Natural selection won't raise the allele's odds of surviving, either. While we may all want to avoid Alzheimer's disease, evolution doesn't care about our desires. Alleles get spread over the generations if they help people reproduce more. An allele that lowers the odds of dementia at age seventy doesn't help at all. Within a few generations, the variant you paid so dearly to give your children might disappear entirely.

When people wring their hands about what genetic engineering might do to the human gene pool, they often forget that it's actually more like a human gene ocean. If I strain my science-fiction faculties to their limit, I can imagine a worldwide dictatorship that forces every parent on Earth to submit to CRISPR and introduce the same variants into every child. But just because I can imagine the movie doesn't mean I think it's likely.

Gene-pool arguments are flawed for another reason. They treat the collective DNA of our species as if it were inscribed in stone tablets long ago and passed down unchanged ever since. In fact, the human gene pool has always been changing, and will continue to change, regardless of what we do to it. Each one of the 130 million babies born each year gains dozens of new mutations. Some will gain mutations so toxic that they will never get the chance to have children of their own, while others will choose not to. The rest will pass down some of those new mutations to future generations. Some mutations will lead to slightly larger families, on average, and those will become more common in the human gene pool. Over time, other mutations will fade back. The variants that succeed in one part of the world will sometimes be different from those in other places. Some variants are beneficial at high altitudes but not low; some tend to spread in places with malaria and not in places free of the parasite.

Amidst all this churning change, another transformation has also been steadily occurring in our species. As Muller feared, the human gene pool is indeed gaining a burden of harmful mutations. Muller first proposed
the concept of a mutation load at a time when scientists knew next to nothing
about the biological details of mutations. For the most part, Muller just relied on math. It wasn't until long after his death in 1967 that biologists began making precise measurements of the mutation load by surveying people's DNA. It turns out that our species does carry a substantial burden of harmful genetic variants. While extreme mutations are rare, mildly harmful ones are abundant. They are accumulating in our DNA as we find more ways to shield ourselves from suffering and death.

In 2017, Alexey Kondrashov, a geneticist at the University of Michigan, got so worried about the emerging research on our mutation load that he published a book-length warning, called
Crumbling Genome.
It's possible, Kondrashov said, that each generation will inherit a more burdened gene pool than the previous one. Depending on how quickly the mutation load grows, it might someday drag down our collective health.

Muller's Germinal Choice plan might sound absurd, but Kondrashov believes that the mutation load is a threat we cannot ignore. He suggests there are some ethically uncomplicated things we might do today to defend against it. As men get older, their sperm accumulate more mutations. If they freeze sperm as young men, they can pass on less of a burden to future generations. If the mutation load gets worse despite such measures, our species might have to use CRISPR or some other gene editing tool to plug the rising tide.

“
I hope that ‘War on Mutation' is declared soon,” Kondrashov wrote.

The future probably won't match the most extreme visions we can dream up. But it will disorient us. It will take what we thought were iron laws of heredity and stretch them in strange figures. In fact, the disorientation has already begun.

In the early 2000s, for example, fertility doctors began producing so-called
savior siblings. When children developed leukemia or some other disease requiring a bone marrow transplant, some families would go through rounds of in vitro fertilization until they produced a baby with just the right combinations of HLA alleles to be a donor.

In 2011,
a seventeen-year-old Israeli girl named Chen Aida Ayash was killed in a car accident. After her death, her parents asked for doctors to collect some eggs from her cadaver. They had to go to court to get permission, explaining to a judge that they wanted to fertilize Chen's eggs, after which Chen's aunt would bear them to term. After her own death, Chen would give her parents grandchildren.

These cases are carrying us into realms where old customs and rules start to sputter and fail. The words that we used to use to talk about heredity lose their old meanings, or take on new ones. And when people fight about those words, judges struggle to figure out who is right. In 2012, the US Supreme Court found itself in such a bind when they heard a case brought by
a Florida woman named Karen Capato. Her husband, Robert, was diagnosed in 1999 with esophageal cancer. He immediately began depositing his sperm in a sperm bank, so that if his chemotherapy left him infertile, Karen could still become pregnant through in vitro fertilization. The treatment failed, and Robert died in 2002.

Karen did not have his frozen sperm destroyed after his death. Nine months later, she used some of it to fertilize her eggs and gave birth to twins. Karen filled out paperwork so that the twins could get Social Security benefits for their father's death. But the Florida state government rejected her application. They pointed to their state laws, and held that children conceived after the death of their father couldn't inherit his personal property.

After hearing Karen Capato's appeal, the Supreme Court ended up ruling against her. But their 9–0 decision came only after hours of maddening oral arguments. The judges and the lawyers got bogged down in debates over the definition of a child. It was clear that the congressmen who laid down the rules about inheritance in the Social Security Act in 1939 couldn't have imagined children being conceived months after their father's death. “They never had any inkling about the situation that has arisen in this case,” grumbled Associate Justice Samuel Alito.

If genetic engineering ever becomes commonplace, the Supreme Court will probably find itself in even harder quandaries, where old laws provide even worse guidance to the new ways of tinkering with heredity.

A few cases have been brought by children against their parents for allowing them to be born with congenital diseases. According to these “wrongful birth” lawsuits, the parents were negligent for ignoring tests on the fetus before birth and going ahead with it anyway. Some ethicists now wonder if children in the future may sue their parents for not using mitochondrial replacement therapy to cure Leigh syndrome or some other devastating mitochondrial disease. If parents have the genome of an embryo sequenced and choose not to edit out a variant that puts people at a high risk of dementia, their children might hold them accountable.

It's hard to say if such children would win. In some forms of mitochondrial replacement therapy, the nucleus from an unfertilized egg is moved to a new egg. Only then do doctors fuse a sperm to it. For a child in this case to claim they were harmed by coming into existence, they have to show they're worse off as a result of the procedure. But if not for the therapy, somebody else would have been born—in other words, an embryo that inherited a different combination of genetic variants from its parents.

As a society, we are probably not prepared to handle these ethical dilemmas. But there are even more profound challenges to our concepts of heredity coming fast over the horizon. Fertilizing eggs months after a father's death seems strange because it stretches the timing by which one generation produces the next. But the process of heredity that takes place is utterly conventional. Karen and Robert Capato, for instance, produced lineages of cells in their bodies that gave rise to germ cells. They shuffled their chromosomes through meiosis as cells have done for billions of years. The germ cells combined, joining their genes together to produce embryos. And then the embryos developed into children with germ cells of their own.