Gene editing: Time has come to engineer DNA to block transmission of inherited disorders, say scientists

It is the last great taboo of genetic medicine but some scientists now believe the time has come to consider the deliberate engineering of human eggs, sperm or embryos in order to block the transmission of inherited disorders by altering the DNA of all subsequent generations of affected families.

Germ-line gene therapy is banned in Britain and 14 other European countries but recent advances in the technology of gene-editing has meant that society should once again debate the idea of deliberating changing the genomes of future generations of children, scientists said.

“This technology is poised to transform preventive medicine. Rather than talk about the possibility of banning alteration of the human germ-line, we should instead be discussing how to stimulate ways to improve its safety and efficacy,” said Professor George Church, a leading geneticist at Harvard Medical School in Boston.

“Banning human germline editing could put a damper on the best medical research and instead drive the practice underground to black markets and uncontrolled medical tourism, which are fraught with much greater risk and misapplication,” Professor Church said.

On 1 December in Washington DC, the national science academies of the United States, China and Britain will host an international summit on gene editing, focussing on the safety and ethics of genetically engineering human “germ cells” to eliminate inherited illness – a development that will inevitably raise the prospect of creating genetically-enhanced “designer babies”.

Some experts have voiced concerns about the use of gene editing on human eggs and embryos, saying it will have unpredictable consequences on future generations, making it dangerous and ethically unacceptable.

However, Professor Church and many other scientists behind the development of a revolutionary gene-editing technology, called Crispr-Cas9, believe these concerns should not prevent research that could one day lead to effective treatments for crippling and incurable conditions, such as muscular dystrophy and Huntington’s disease.

Writing in the journal Nature, Professor Church said the ethical arguments against germ-line gene therapy – that it is unsafe, irreversible and fails to have the consent of the infant involved – do not stand up to scrutiny.

“Human germline editing is not special with respect to permanence or consent. Replacing deleterious versions of genes with common ones is unlikely to lead to unforeseen effects and is probably reversible. Even if the editing was difficult to reverse, this would not be especially unsafe compared with other commonly inherited risks,” Professor Church said.

As regards safety, the Crispr-Cas9 method appears to be remarkable accurate in its ability to “find and replace” precise segments of DNA, with an error rate of less than 1 in 300 trillion, Professor Church said. Other error-correcting techniques could reduce this rate still further, by tenfold at least, he said.

Prospective parents who are known to carry defective genes can at present be offered pre-natal genetic diagnosis to select IVF embryos that are free of familial mutations. But this option is not available in every situation where there is a risk of passing on defective genes and inherited disorders – such as a parent who is carrying two copies of a DNA defect.

Professor Church also dismissed fears that allowing germline gene therapy to treat inherited disorders will automatically lead down a “slippery slope” to genetic enhancement with “beneficial” traits, such as sporting prowess, intelligence or physical appearance.

“Those who want to ban human germline editing should also consider that such a move would do little to allay concerns about ethically dubious attempts to enhance humans,” Professor Church said.

“To think that there is not already a cadre of IVF clinicians poised to engage in such practices, perhaps even supported by governments, is to ignore, for example, the history of doping in sport,” he said.

“These kinds of ambitious individuals and institutions are unlikely to be dissuaded by an agreement made on their behalf by others with a different view,” he added.

Jennifer Doudna, a molecular and cell biologist at the University of California, Berkeley and a pioneer of Crispr-Cas9, said that a complete ban on germ-line gene therapy might prevent breakthroughs in some of the most distressing and difficult medical disorders.

However, Professor Doudna also said the time has not yet come to allow scientists to forge ahead with germ-line human engineering until more research has been done.

“Human germline editing for the purpose of creating genome-modified humans should not proceed at this time, partly because of the unknown social consequences, but also because the technology and our knowledge of the human genome are simply not ready to do so safely,” Professor Doudna.

Conventional gene-therapy: clinical trials are already planned or underway to develop a “functional cure” for HIV patients using modified T-cells, as well as for a genetic blood disorder called beta-thalassaemia

Germ-line gene therapy: by altering the genes of eggs or embryos, it might be possible to block the transmission of inherited diseases such as Huntington’s or muscular dystrophy to all subsequent generations within an affected family.

Animal organ transplants: scientists have eliminated viruses from within the genome of pigs using gene-editing techniques, enabling gene-edited pig organs potentially to be used in human transplant operations.