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Germline Tinkering Sparks More Controversy

By Michael Cook

The ability to “edit” the genome has already seen Chinese scientists accidentally introduce mutations into human embryos.

The single most controversial development in biology in 2015 is a relatively cheap, easily manipulated technology for modifying the human genome. Called Crispr, this tool allows scientists to “edit” the genome by deleting or adding DNA sequences. In just a couple of years, frenetic activity in labs around the world has taught scientists how to target and activate or silence specific genes.

The implications for plant, animal and human biology are immense. For humans, Crispr opens up a panorama of dramatic cures – and even enhancement of the human genome.

But it is also quite troubling. Gene editing with Crispr only began in 2013, but within 2 years it was already clear that the ethical questions hanging over it were huge.

Tinkering with the human germline has been off-limits for decades. Since the 1970s there has been a consensus that scientists should not “play God” by creating “designer babies”. This has been codified in UNESCO’s Universal Declaration on the Human Genome and Human Rights, which states that germ-line interventions “could be contrary to human dignity”.

However, it appears that the established consensus by scientists on an impossibility started to break up as soon as it became possible.

In March two statements appeared in the world’s leading science journals. In Nature, Edward Lanphier, a leading figure in Crispr-related research, and four colleagues called for a moratorium on modifying the genome of eggs, sperm or embryos. They opposed “germline modification on the grounds that permitting even unambiguously therapeutic interventions could start us down a path towards non-therapeutic genetic enhancement”.

However, a statement in Science by Crispr experts, establishment scientists and bioethicists was more accommodating. They only urged that germline modification be “strongly discouraged”, “even in those countries with lax jurisdictions”.

Guess what? Within a month scientists in a country with a lax jurisdiction, China, announced that they had used Crispr technology to genetically engineer human embryos. Researchers at Sun Yat-sen University in Guangzhou obtained defective human embryos from an IVF fertility clinic and targeted a gene that can cause beta thalassemia, a serious blood disorder.

But the results were disappointing. The researchers injected 86 embryos and examined them after 48 hours when they had grown to eight cells. Of these, 71 survived and 54 were analysed. Only 28 had successfully spliced the target gene, and only a fraction of these contained the correct replacement gene.

They also found that a number of “off-target” mutations were introduced by Crispr. Had these been viable embryos, Crispr would have caused much more illness than it cured.

Notwithstanding these dismal results, some scientists are bound to press on in the hope of improving the technique. In China, research will proceed willy-nilly because there is little ethical oversight. In the United States and Britain, scientists will have to wait for government approval.

A fascinating ethical gap is opening up between the two countries. The director of the US National Institutes of Health (NIH), Francis S. Collins, has declared forthrightly that the NIH would not fund such research. He cited “the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications”.

But in Britain it was hard to find scientists or bioethicists who were opposed, let alone alarmed, by the news. “It’s no worse than what happens in IVF all the time, which is that non-viable embryos are discarded,” said bioethicist John Harris. “I don’t see any justification for a moratorium on research.” And Oxford bioethicist Julian Savulescu, the editor of the Journal of Medical Ethics, even declared that Crispr research on human embryos is “ethically imperative”.

One of the UK’s leading stem cell researchers, Robin Lovell-Badge of the MRC National Institute for Medical Research in London, was almost enthusiastic. “I disagree with a moratorium, which is in any case unlikely to work well,” he said. “Indeed I am fully supportive of research being carried out on early human embryos in vitro, especially on embryos that are not required for reproduction and would otherwise be discarded.”

It’s déjà vu for observers of bioethical trends. The bitter debate over human embryonic stem cells went on for years. Crispr is sure to throw petrol on the bonfire all over again.

Michael Cook is editor of the online bioethics newsletter BioEdge.