CRISPR gives us the power to short-circuit evolution. What now?

Dina Temple-Raston

THE WASHINGTON POST – In November 2018, a Chinese scientist named He Jiankui shocked the world when he announced that he deliberately tweaked the genes of two embryos to make them resistant to the AIDS virus, HIV.

He did that using CRISPR gene editing, an ingenious system that allows little molecular scissors to snip bits of DNA. Molecular scissors aren’t new – scientists have been using them to cut DNA since the 1970s – but CRISPR is considered a snip above because its little scissors are so flexible, it’s infinitely easier to target specific DNA sequences.

He’s “goal was to make the gene inoperative and thus deprive HIV of that gateway for infection”, Stanford University bioethicist Henry T Greely wrote in his new book CRISPR People: The Science and Ethics of Editing Humans. “Two edited embryos, of nonidentical twin sisters, were transferred into their mother’s uterus sometime in late March or early April 2018. Sometime in October, somewhere in China, they were born.”

The birth of those twins marked the first time scientists tinkered with the human genome to pass some trait along to the next generation. In a very real sense (and this was the problem), He and his team were using CRISPR to short-circuit over a billion years of evolution. They created CRISPR babies, unleashing fears that the next inevitable step would be designer babies.

CRISPR People is an accessible, clearly written, fact-filled analysis of a new biological frontier. Readers will come away not only with a deep understanding of CRISPR and how it works, but also with an appreciation of how a Chinese scientist created the first gene-edited humans and what that means for the rest of us. Greely believes that He’s experiment was nothing less than “a cross between bad fiction and reckless fiasco, shrouded in a deep fog of secrets”.

CRISPR People is less gossipy and character-driven than Walter Isaacson’s recent book The Code Breaker. Jennifer Doudna and Emmanuelle Charpentier, who won the 2020 Nobel Prize in chemistry for their CRISPR work, make mere cameo appearances here. Greely chosen instead to offer a kind of thoughtful dispatch from the front lines. This book isn’t about how CRISPR came to be but instead about how we might think about it now that it has arrived.

If this bioethical discussion feels vaguely familiar, it should. We’ve been here before, about a quarter-century ago. Back then the conversation swirled around a little sheep named Dolly. In 1996, researchers at the Roslin Institute cloned a cell taken from the mammary gland of a six-year-old Finn Dorset sheep and an egg cell taken from a Scottish blackface sheep, and the result was Dolly.

“Her birth was kept secret until the researchers… could publish their scientific paper on her,” Greely wrote. “I don’t remember what I said to my dean, but I do remember thinking ‘Things are about to get interesting.’” Greely said he had the exact same reaction when he heard about He’s experiment in China.

Before Dolly, the thought of cloning a mammal was the stuff of science fiction, but – fast-forward 25 years – it wasn’t the feasibility of genome editing that was in question before He decided to edit human embryos. Scientists have known for some time that human eggs undergoing in vitro fertilisation could be genetically altered.

What no one seems to have expected was that someone like He would appear on the scene, jettisoning the consensus of every major scientific and medical organisation to try his hand at editing the human code of life.

Greely made clear that he thinks what He did was wrong. But he doesn’t think that genome editing should be banned. Quite the contrary. Some 7,000 human diseases are caused by genetic mutations, and CRISPR could go a long way toward curing them. “CRISPR might be used to change DNA of people with sickle-cell disease to a version that would give them normal hemoglobin and hence normal blood,” Greely explained, “blood that would not cause an always painful and often life-threatening condition.”

In fact, he added, he has a colleague at Stanford who is doing exactly that.

The difference between Greely’s colleague and He is simple: The Chinese scientist decided to use CRISPR on human embryos when, one could argue, there was no pressing medical need to do so.

The HIV/AIDS infection rate in China is nowhere near what it is in the West. But in Hunan, He’s home province, HIV/AIDS is particularly prevalent, so that might have motivated his decision to focus on the virus. It might explain, too, why at least initially his “experiment” was celebrated in China. Scientists from around the world then weighed in, expressing horror at what He had done. The Chinese government then said it too was appalled, and He was tried and sentenced to three years in jail.

Greely, who had a front-row seat to many of the events in his capacity as director of the Stanford Center for Law and Biosciences, revealed to readers how He’s experiment came to be. The Chinese scientist, by Greely’s telling, was more motivated by the idea of using CRISPR to edit the human genome than by some burning desire to wipe out the AIDS virus.

In fact, He initially thought he would use CRISPR to focus on a gene that has been found to confer substantial immunity to coronary heart disease. It was only after ruling out several other genes that he turned his attention to HIV/AIDS. He submitted a medical ethics approval application to the Shenzhen HarMoniCare Women and Children’s Hospital in the spring of 2017 and received permission to move forward with his research a short time later. Then he set out to find the perfect subjects.

“He had contacted an HIV/AIDS support group called the Baihualin China League and sought their support to find couples who would be willing to volunteer to try to have a ‘genetically’ HIV-resistant baby,” Greely wrote. “The group’s founder reportedly introduced about 50 families to He’s team (something he now regrets).”

Eventually, eight married couples in which the father had been infected with HIV and the mother had not agreed to participate. “I stand by the comments I made to the press just after the news broke,” wrote Greely. “The experiment was ‘criminally reckless’ as well as ‘grossly premature, and deeply unethical.’ “

Citing the Nuremberg Code, aimed at protecting human subjects from the kind of cruelty and exploitation that prisoners endured in concentration camps, regarded as the cornerstone document on human research ethics, Greely convincingly concluded that the risk-benefit ratio for such an experiment is simply too high.

Still, while He’s rush to move heritable genome editing into humans was reckless, Greely wrote, human genome editing isn’t inherently wrong. Under rare circumstances, he said, it can be used – but only when there are no good alternatives. Genome editing is too new and may not work as well as people think it does. For example, He may have fixed one gene only to have introduced a problem somewhere else inside the twins who were born with the edited genome. They may have resistance to HIV but be more susceptible to other viruses.

Greely made clear that He was an ambitious scientist who became a modern-day Victor Frankenstein, but also makes clear that the Chinese scientist is an outlier. The scientific community, he wrote, has been very good at policing its own and will need to step up as this technology develops.

“Most scientists, and hence most science, are much more rule bound, constrained by the needs of getting and keeping jobs, tenure, and most importantly grants, as well as wrapped, in most countries, in many bureaucratic threads of control. But He happened, and Science needs both to act to minimise the harm he has caused and to be seen to be doing so.”