The Promise and the Reality of Gene Editing

The Crispr Revolution and the New Era of Genome Editing
By Kevin Davies

In July 2019, MIT Technology Review took a break from its usual beats, such as artificial intelligence and biotechnology, to offer some news from the world of book publishing.

“The Crispr story has arrived for the grand telling as a miracle of our age,” the journal announced. “The proof? At least four popular, mass-market books about the DNA-snipping technology are underway.”

Fifteen months have passed, and now I struggle to remember July 2019. Like many, I am experiencing a pandemic-induced amnesia of the Before Times. I turned to this newspaper’s archive for help, and there I discovered that July 2019 was the month that the United States women’s soccer team won the World Cup. I looked at the photograph of Megan Rapinoe celebrating her team’s victory and marveled at how fiercely she embraced her teammates, screaming in unmasked joy, before a stadium filled with socially undistanced fans. We did that kind of thing once.

July 2019 was also a time when we eagerly looked forward to books about Crispr. And now, deep in the pandemic, the first of the four promised ones — “Editing Humanity,” by Kevin Davies — has finally arrived.

Davies offers a history of what he calls “one of the most remarkable scientific revolutions we have ever seen.” I can’t say what it would have been like to read “Editing Humanity” back in July 2019. But reading it now — at a time when the coronavirus is killing nearly a thousand Americans every day — is a disorienting experience. If Crispr is indeed a miracle of our age, it seems in this time of carnage to be an impotent one.

Davies recounts the history of Crispr in detailed yet breezy prose. He starts, as one should, back in the 1980s when scientists discovered Crispr and had no idea what they were looking at. All they knew was that some bacteria carried strange repeating bits of DNA. These were not genes, but their repeating pattern suggested they weren’t just random junk. Francisco Mojica, a microbiologist at the University of Alicante, dubbed these enigmatic regions “clustered regularly interspaced short palindromic repeats.” Mojica and soon everyone just called them Crispr.

In the mid-2000s, it became clear what the microbes were doing with Crispr. Like us, microbes are beset by viruses, and they have evolved their own immune system to defend against them. The Crispr region of their DNA encodes molecules that can recognize viral genes and then cut them into harmless pieces before they can take over their host.

Within a few years, scientists figured out how to harness this natural genetic engineering. They created artificial Crispr molecules that could target the genes of a cell instead of the genes of a virus. They could snip out a particular bit of the gene, which could then stitch itself back together. Subsequent research showed that it was possible to swap in a new piece of DNA for the excised chunk. The process proved more accurate than previous gene-editing technologies. Plus, it was easy and cheap.

Three years ago, one of the pioneers of this work, Jennifer Doudna of the University of California, Berkeley, recipient of the 2020 Nobel Prize in Chemistry, covered much of this early history in her first-person account, “A Crack in Creation,” written with her colleague, the Columbia University biochemist Samuel H. Sternberg. Now Davies, the author or co-author of four previous books and the executive editor of The Crispr Journal, digs deeper into this same history with a journalist’s relish.

Davies lays out how Crispr could become an economic giant. Millions of people suffer from diseases that are the result of inheriting dangerous mutations. People with sickle cell anemia, for example, inherit two faulty genes for hemoglobin, the oxygen-ferrying molecule in red blood cells. After many decades of research, doctors have no cure for the disease, only stopgap measures to slow its progress and ease the symptoms.

Crispr offers a new possibility: Remove the bone marrow stem cells that give rise to red blood cells, erase the mutation in them that causes sickle cell anemia, and put them back in a patient’s body. In theory, they should produce healthy red blood cells and cure the disease. This scenario is no longer theory: Volunteers with sickle cell anemia have had their cells edited in clinical trials, and it’s entirely possible that the treatment may be approved for general use in the next few years.

“The term ‘Holy Grail’ is overused in science,” Davies writes, “but if fixing a single letter in the genetic code of a fellow human being isn’t the coveted chalice of salvation, I don’t know what is.”

But genetic medicine is only one field where Crispr will likely find applications. It could potentially allow scientists to make far more sophisticated tweaks to the DNA of animals and plants than traditional technologies allow. New strains of crops and new breeds of livestock could arise.

In 2018 — a year after Jennifer Doudna published “A Crack in Creation” — she and her colleagues were blindsided by the biggest threat to Crispr’s promise: A Chinese scientist named He Jiankui had edited the DNA of human embryos. He had them implanted in women’s bodies, and nine months later the first Crispr babies were born.

Davies offers a deeply researched look at how He managed this dubious feat, made possible by massive funding from the Chinese government for biotechnology research. When He gave a lecture in Hong Kong days after the news broke, Davies was in the room.

The ethical breaches that He committed were many, but the worst was that his editing was sloppy. Reviewing what little evidence he divulged, experts suspect he cut the wrong bits of DNA, and the children who inherit his mistakes will have to endure whatever harm comes from it for the rest of their lives. But Davies doesn’t limit the blame to He. The Chinese government enabled He with lavish support and surely must have known what he was up to. A number of Western scientists either helped him along the way or didn’t sound the alarm when He told them about his plans. If Crispr researchers expect the world to let them police themselves, this was a disappointing display of self-regulation.

Doudna and other scientists gathered over and over again at chin-stroking panels in the years that followed. They worried not just that rogue scientists might harm children with faulty editing. What if rich parents sought to enhance their children with genetic upgrades? They issued reports concluding that there were almost no situations in which using Crispr on embryos could be justified — but offered no concrete ways to stop it from happening.

Just a couple of years after He Jiankui’s brief burst of fame, it’s hard to imagine a time when the hypothetical possibility of Crispr babies was an urgent crisis. Our children now face far bigger threats than the vague possibility that someone may try to tinker with their baby’s DNA to score better on the SATs. The pandemic of 2020 has disrupted the education of a billion children, according to the United Nations. A hundred million children may be pushed into extreme poverty by the coronavirus’s economic ravages.

We will get past Covid-19 eventually, but children will suffer its consequences for years to come. Many will lag behind in school or drop out completely; malnutrition and resurgent diseases will dim their prospects even further. Meanwhile, the ultrawealthy are building bespoke one-room schoolhouses where their children will enjoy private, virus-free tutoring. We didn’t need Crispr to create this dystopia. And Crispr won’t give us an easy way out.

I certainly don’t blame Davies for the timing of his book’s publication. It was still in production when the pandemic struck, allowing him to slip in a few Covid-19 updates toward the end. Davies recounts how Crispr researchers pitched in to help fight the virus. Doudna and another major researcher, Feng Zhang, both focused on testing.

Doudna quickly set up a large Covid-19 testing center at Berkeley that could process a couple of thousand tests a day. Meanwhile, Doudna and Zhang both worked on Crispr-based tests that could deliver fast results at home.

Davies leaves out the most important fact about these projects, one that’s glaringly obvious by its omission: For the entire pandemic, the United States has been floundering in a testing crisis, and these two masters of the Crispr universe did not manage to fix it.

The United States is nowhere near the millions of tests a day that many public health experts say it needs to stay safely reopened. Its backlog is so dire that it can take a week or more for many people to get their results. Doudna’s pop-up testing center was an impressive feat of swift mobilization, but it can handle only about a thousandth of the tests that the United States should be running. National planning is essential to fixing this disaster, and no flashy technology can substitute for it.

What’s more, Doudna’s testing center doesn’t even use Crispr-based tests. Instead, she and her colleagues use a tried-and-true method called PCR. Though scientists have been diligently working on Crispr-based tests for years now, they’re a long way from the dream of a quick exam you can carry out at home.

The dream seems straightforward, but its path to existence — through experiments, research grant applications, investment pitches, regulatory approval, manufacturing agreements, supply chains and all the rest — is long and twisted. Decades from now, when Crispr is no longer a new sensation, I suspect this will be the story that writers tell about it.

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