The rush to edit the first human genome

Human genome editing – the process of changing a human’s genetic makeup to cure or remove genetic conditions – is an issue fraught with controversy. There are scientific concerns that genetic changes can give unpredictable results, while the ethics of selectively changing human genomes are also problematic.

Recent advances in the technologies used for genome editing have strengthened the scientific case for its use in medicine. A technique known as Crispr allows scientists to change DNA sequences far more precisely than was previously possible. Combined with improved knowledge of the genetic basis of inherited conditions, this could eventually lead to the eradication of many debilitating disorders. However, the ethical concerns surrounding genome editing’s use remain.

Premature and reckless

Until recently, this discussion of ethics involved only hypothetical problems. But two cases from the last few months have accelerated the debate.

Late last year, Chinese scientist He Jiankui caused uproar in the scientific community when he announced the birth of gene-edited twin girls. He used Crispr to make the girls, whose father was HIV-positive, resistant to the virus. But his work was condemned worldwide as premature, reckless and unnecessary.

This week, New Scientist reported that a Russian biologist, Denis Rebrikov, intends to use Crispr on the embryos of five deaf couples who want to have hearing children. His proposed treatment would involve editing DNA in embryos to correct a common mutation that lead to inherited deafness. “It is clear and understandable to ordinary people,” Rebrikov told New Scientist. “Each new baby for this pair would be deaf without gene mutation editing.”

But this intervention, too, has been widely criticised. Lydia Teboul, the head of molecular and cellular biology at the Harwell Institute in Oxfordshire, said that similar work in laboratory animals had proven unpredictable and prone to errors. She said: “This means that current genome editing tools are not ready to be applied to human embryos.”

The case for Rebrikov’s proposed treatment is stronger than for He Jiankui’s. Gene editing is the only viable way for two parents with the same deafness-causing mutation to have hearing babies. He’s work is likely redundant because medical treatment can already prevent HIV-positive parents from passing on the virus to their children. There is also some merit in that Rebrikov, unlike He, is openly discussing his plans before carrying them out.

Technical and ethical problems

However, the scientific community remains cautious. Robin Lovell-Badge, a stem cell biologist at the Francis Crick Institute, has called for strict controls to regulate the use of genome editing in humans. “This is not something that any individual can decide – the situation is just too complex,” he said. “There are technical problems to be overcome.”

One such problem is that, for genome editing in human embryos to be successful, the affected gene must be corrected in every cell. Lovell-Badge says that Rebrikov has yet to convince his colleagues that he is able to address this.

Another issue is that the gene being corrected may have additional roles not yet identified. Biological processes are often the result of a suite of genes interacting with each other, and ruling out such interactions requires extensive research.

Then there is the issue of the effect ‘curing’ deafness, which is not a life-threatening condition, might have on other deaf people. Harlan Lane, a psychologist at Northeastern University, has called existing therapies for deafness a form of “cultural genocide”. Darren Griffin, professor of genetics at the University of Kent thinks Rebrikov’s work could make matters worse. “A public debate is essential and the deaf need to be heard,” he said.

International framework

Many scientists feel there needs to be international consensus on the use of genome editing therapies before they are attempted in humans. A new international commission on human genome editing, led by the UK’s Royal Society and the United States’ National Academies of Science and Medicine, was launched earlier this year. It will develop an international framework to be used when considering whether genome editing therapies should be allowed.

Meanwhile, new research published last month showed that people with the type of HIV resistance given to the twin girls in He Jiankui’s work have a shorter life expectancy. Lovell-Badge said “this shows once more that He Jiankui was foolish to choose CCR5 to mutate in his attempts at germline genome editing. We simply do not yet know enough about the gene.”

Lydia Teboul, Darren Griffin and Robin Lovell-Badge’s quotes were compiled by the Science Media Centre here and here.