Saturday, December 1, 2018

World’s first gene-edited babies announced by a scientist in China

AP Photo/Mark Schiefelbein
Via newscientist.com by Alice Klein and Michael Le Page

A woman in China has given birth to two genetically edited baby girls, according to the Associated Press news agency. The aim of the experiment was to create children who are immune to HIV, but it hasn’t yet been independently reviewed or verified.

The experiment has been widely condemned as unethical, even by those who are in favour of using gene editing in eggs, sperm or embryos to prevent diseases in children if it can be done safely.

“If true, this experiment exposes healthy normal children to risks of gene editing for no real necessary benefit,” says ethicist Julian Savulescu at the University of Oxford. “There are many effective ways to prevent HIV in healthy individuals.”

“There is no pressing need for this – it’s totally inappropriate,” says Greg Neely at the University of Sydney, Australia.

HIV enters and infects cells by binding to a protein on the surface called CCR5. The team in China, led by He Jiankui of Southern University of Science and Technology of China in Shenzhen, says it has used the CRISPR gene editing technique to try to disable the gene for CCR5.
 

 
Edited genes

One aspect of the experiment that has come under criticism is that we don’t yet know if it is safe to delete both copies of the CCR5 gene – which is involved in immunity – in every cell of the body. “We don’t know what the full effects will be,” says Neely.

Seven pairs of men and women reportedly took part in the experiment. All of the men were HIV-positive, and, according to the Associated Press, each couple was offered free IVF treatment in exchange for participating in what was described on ethical consent forms as an “AIDS vaccine development programme”. The team behind the work says the couples were fully informed about the experiment.

The sperm from each man was “washed” to rid it of any HIV, and then injected into eggs extracted from their partners. Next, the CRISPR gene editing machinery was injected into the resulting embryos.

In total, the experiment produced 22 embryos. To check that the CRISPR gene editing had worked, a single cell was removed from each embryo and analysed. He says that 16 embryos had successfully been edited, 11 of which were implanted. Only one pregnancy was successfully achieved, and it produced twins.

Of these twins, one is said to have had both their copies of CCR5 disabled. That means that their body won’t make the CCR5 protein, and their cells should be able to resist infection with HIV.

However, according to the Associated Press, the embryo for the second twin only had one copy of CCR5 disabled. This raises ethical questions – why was this embryo still implanted in its mother, given the known risks of gene editing, and the fact that this individual will still be vulnerable to HIV?
 
Safety questions

How editing the CCR5 genes of embryos will help future children is unclear. In the case of the twins, their mother doesn’t have HIV and their father’s HIV is apparently well-controlled. Simple measures should be sufficient to prevent the father from passing the virus to his children.

The vast majority of biologists who use CRISPR gene editing think it is far too early to attempt to use it for editing human embryos because it is still far from clear if it is safe.

In several studies, human embryos have been genetically edited to see if CRISPR works in people, and then destroyed rather than being implanted. The largest of these studies, done in the US, was widely reported as being successful but in fact the findings have been questioned by many in the field and remain highly controversial.

The greatest risk is that the gene editing doesn’t take place until after the fertilised egg begins dividing, meaning only some of the cells have the desired alteration and the body is a “mosaic” of altered and unaltered cells. This is reportedly the case with the second twin.

The other major risk is that the CRISPR gene editing machinery causes mutations in other genes. The team in China claims this hasn’t happened, but there hasn’t been any independent confirmation of this yet.

If the science progresses, says Savulescu, it might be reasonable to try using CRISPR in embryos with lethal genetic mutations. “Gene editing for this group might be life-saving; for the [twins], it is only life risking.”

However, it is already possible to prevent children inheriting most serious diseases by screening IVF embryos before implanting them. There are very few cases where gene editing would be the only option, though for religious reasons some regard “curing” an embryo’s mutations as preferable to discarding them.

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