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Editing the human race

Editing the human race

A new gene-editing technique called Crispr may enable scientists permanently to alter the human gene pool

What is meant by “gene editing”?

It’s a kind of microsurgery applied to the genes of a living cell for the purpose of correcting harmful mutations. Scientists hope it could be used to combat sickle-cell anaemia, for example, a debilitating, often deadly disease, caused by a mutation in just one of a patient’s three billion DNA base pairs. They also hope to edit patients’ immune cells in such a way as to make them attack cancers. Yet despite huge advances in the analysis of the human genome, they have hitherto lacked sufficiently precise gene-editing tools to make much headway. Until now.

What has changed?

In the past three years, a new generation of genetic engineering techniques have been developed that are so quick, so cheap and so easy to use, they’re transforming the way gene editing is done. The newest, simplest and least expensive of these is one called Clustered Regularly Interspaced Short Palindromic Repeats, or Crispr (pronounced “crisper”). Developed at the University of California, Berkeley, in 2012, it essentially enables scientists to snip out and splice a piece of any organism’s DNA, much as a film editor would cut and splice an old film reel.

How does Crispr work?

Crispr is actually a naturally occurring defence mechanism used by certain types of bacteria to protect themselves from infection by viruses. One part of this mechanism involves the bacterium identifying the DNA of an invading virus and creating matching sequences of that DNA within its own genome. This enables it to target the virus the next time it attacks. The other part of the mechanism is an enzyme called Cas9 which, acting like a pair of molecular scissors, slices up the virus thus identified. Scientists now realise that Crispr – or Crispr-Cas9, to give its full title – can be engineered to slice not just viral DNA but any target gene within a living cell. And once the gene has been cut out, it can be replaced with another gene (if needed) before the ends of the DNA are stitched neatly back together. The entire process takes just days and costs as little as $30. “In the past, it was a student’s entire PhD thesis to change one gene,” says geneticist Bruce Conklin. “Crispr just knocked that out of the park.”

And the implications of all this?

They’re huge. Crispr is already being used to make certain crops invulnerable to killer fungi, and to create a strain of mosquitoes with malaria-blocking genes that the insects pass on to some 99.5% of their offspring. Progress in tackling disease in humans will take longer, but there has been some preliminary success with experiments involving sickle-cell anemia, HIV and cystic fibrosis. But the technique’s most promising application is as a potential cure for hereditary diseases. And this is where the technique starts to become highly controversial.

Why is it so controversial?

In theory, scientists could use Crispr to cure single-gene defects such as Huntington’s disease, by editing out the disease-carrying gene from the DNA of a fetus in the womb. And unlike the edits done on genes found in somatic cells – which make up most of the human body – edits done on genes found in egg and sperm cells are passed down through generations, permanently altering the human gene pool and raising the spectre of designer babies, mutants, and scientists “playing God” (see box). In December, an international group of scientists called for a moratorium on human germline editing until Crispr’s risks have been assessed. “Everything I’ve learned here says we’re not ready to be doing this yet,” said Nobel Prize-winning biologist David Baltimore.

But have scientists gone ahead?

Yes. In China, a team at Sun Yat-sen University in Guangzhou has attempted to modify the germline in dozens of human embryos, hoping thereby to snip out a defective gene that causes a deadly blood disorder. The study has caused shock waves across the scientific community – and has also highlighted the practical difficulties of DNA editing in higher organisms. Of the 86 embryos used (all of which were non-viable), a mere four manifested the new gene designed to replace the defective one. Worse still, there were inexplicable mutations in genes that were not targeted by the researchers. “The number of unintended effects is precisely why this technique is not appropriate for use in clinical applications,” bioethics professor R. Alta Charo told Wired magazine.

What are scientists’ biggest fears?

The first worry is whether Crispr can be used safely and without causing unintended genetic changes. Even the best geneticists admit they have only scratched the surface in their understanding of human DNA and the effects that Crispr might have on a person’s 20,000 to 25,000 genes, which interact in ways we still don’t understand. The larger question, of course, is whether scientists should be tinkering with the human gene pool at all. At some point, researchers could switch their attention from curing hereditary diseases to editing supposedly desirable traits into a person’s DNA, such as high intelligence, or tall stature. “Great things can be done with the power of technology – and there are things you would not want done,” said Jennifer Doudna, a Berkeley biologist who co-invented Crispr. “Most of the public does not appreciate what is coming.”

Will there be a moratorium?

That’s unclear. The international conference of scientists who called for the freeze in December included authoritative figures from across the world. But they have no regulatory powers and can do nothing to stop researchers in countries such as China from vigorously pursuing Crispr experiments. Doudna says she dreads the idea of the technique being used on human embryos, but given its potential for preventing children from inheriting debilitating diseases, she believes that step is inevitable. As one of her colleagues observed at a recent meeting of geneticists: “There may come a time when, ethically, we can’t not do this.”

Return of the woolly mammoth?

Crispr has prompted fears that rogue scientists will create “Frankenbabies”, but researchers have been using the technique to resurrect a completely different kind of beast. In March 2015, a team led by Harvard geneticist George Church announced they had successfully copied the genes from the frozen tissue of a woolly mammoth, a species extinct for the past 4,000-odd years, and pasted them into the genome of an Asian elephant. The next step will be to insert those genomes into an elephant egg cell for implantation. The team hopes to create a woolly elephant-mammoth hybrid that can survive in cold temperatures, so that elephants can live comfortably outside of Asia and Africa, where their own existence is threatened by conflict and poverty. What was once purely the realm of science fiction is quickly becoming reality, says Church. “First there was Jurassic Park. Now we have the exact DNA for these ancient species, and, in some cases, we have the appropriate hosts that are pretty close.”

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