THIRD gene-edited baby may have already been born in China

A third baby whose DNA was edited as part of a series of ‘monstrous’ experiments by disgraced scientist He Jiankui may already have been born, experts fear.

Physician and ethicist William Hurlbut spoke out in January over revelations that He had altered the genes of a third embryo, expected to be born in June or July.

With June now behind us, Professor Hurlbut fears that the child may already have been delivered – or, if it hasn’t, that China may decide to keep it quiet when it has.

‘A normal birth is 38 to 42 weeks, and it’s pretty close to the center of that,’ the Stanford University professor told MIT Technology Review. 

 

A third baby whose DNA was edited as part of a series of ‘monstrous’ experiments by disgraced scientist He Jiankui (left) may already have been born, experts fear. Stanford University physician William Hurlbut (right) broke the news about the pregnancy in January

HOW DID DR HE DESCRIBE THE WORK? 

‘The gene editing occurred during IVF, or lab dish fertilisation.

‘First, sperm was ‘washed’ to separate it from semen, the fluid where HIV can lurk.

‘A single sperm was placed into a single egg to create an embryo.

‘Then the gene editing tool was added.

‘When the embryos were three to five days old, a few cells were removed and checked for editing.

‘Couples could choose whether to use edited or unedited embryos for pregnancy attempts.

‘In all, 16 of 22 embryos were edited, and 11 embryos were used in six implant attempts before the twin pregnancy was achieved.’

Professor Hurlbut is not alone in his fears, with some researchers predicting that the secretive Chinese regime will never announce the child’s birth.

Given the controversy surrounding the announcement of the birth of the first two gene-edited infants in November 2018, that seems like a fairly safe bet.

Among the scientists raising their heads above the parapet on the issue is Rosario Isasi, a health and human rights lawyer at the University of Miami whose research and work focuses on the regulation of human genetic technologies.

Ms Isasi says she has been working to encourage scientists in China to speak out and limit the damage from the country’s unethical human experimentation.

She fears that experts in the country are reluctant to speak out, however, and that Beijing is keen to avoid any further publicity over the issue.

‘The government is extremely aware of any transgressions,’ Ms Isasi said in an in-depth article by MIT Technology Review’s Antonio Regalado.

‘They have the Tiananmen anniversary, they have the Hong Kong protests, and they have the CRISPR babies.’ 

Pictured: He Jiankui speaks during an interview at a laboratory in Shenzhen in southern China's Guangdong province in October, 2018

Pictured: He Jiankui speaks during an interview at a laboratory in Shenzhen in southern China’s Guangdong province in October, 2018

WHAT ARE SOME OF THE DOUBTS SURROUNDING DR HE’S CLAIMS?

Several scientists reviewed materials that Dr He provided to the AP and said tests so far are insufficient to say the editing worked or to rule out harm.

They also noted evidence that the editing was incomplete and that at least one twin appears to be a patchwork of cells with various changes.

‘It’s almost like not editing at all’ if only some of certain cells were altered, because HIV infection can still occur, famed Harvard University geneticist Professor George Church said.

Church and Dr Kiran Musunuru, a University of Pennsylvania gene editing expert, questioned the decision to allow one of the embryos to be used in a pregnancy attempt, because the Chinese researchers said they knew in advance that both copies of the intended gene had not been altered.

‘In that child, there really was almost nothing to be gained in terms of protection against HIV and yet you’re exposing that child to all the unknown safety risks,’ Dr Musunuru said.

The use of that embryo suggests that the researchers’ ‘main emphasis was on testing editing rather than avoiding this disease,’ Church said.

Even if editing worked perfectly, people without normal CCR5 genes face higher risks of getting certain other viruses, such as West Nile, and of dying from the flu. 

Since there are many ways to prevent HIV infection and it’s very treatable if it occurs, those other medical risks are a concern, Dr Musunuru said.

There also are questions about the way Dr He said he proceeded.

He gave official notice of his work long after he said he started it – on November 8, on a Chinese registry of clinical trials.

It’s unclear whether participants fully understood the purpose and potential risks and benefits.

For example, consent forms called the project an ‘AIDS vaccine development’ program.

The hospital linked to the controversial project denied approving the procedure and accused Dr He of forgery.

He sparked global controversy in November 2018 when he announced his experiments in a YouTube video.    

Footage claiming in which He claimed to have successfully created gene edited human twins stunned the academic world.

The news dominated The Second International Summit on Human Genome Editing, held in Hong Kong last November.

The summit was meant to provide a forum for debate over the pros and cons of genetically engineering humans.

News that it had already happened taking over proceedings and sparked an international backlash among the scientific community.

He’s actions were universally condemned as unethical and the Chinese government said it had halted work at He’s lab.

It promised it was carrying out an investigation, saying it would take a ‘zero tolerance attitude in dealing with dishonourable behaviour’ in research.

Pictured: In a video he released in November 2018, He Jiankui explained his rationale for CRISPR editing embryos in vitro and then implanting the embryos in a Chinese woman.

Pictured: In a video he released in November 2018, He Jiankui explained his rationale for CRISPR editing embryos in vitro and then implanting the embryos in a Chinese woman.

Between March 2017 and November 2018, He forged ethical review papers and recruited eight couples to participate in his experiment, resulting in two pregnancies. 

News of a third child emerged thanks to questioning by British biologist Robin Lovell-Badge, who prised news of another CRISPR baby out of He 

‘Just to be clear, are there any other pregnancies with genome editing as part of your clinical trials?’ the Francis Crick Institute researcher asked.

‘There is another one, another potential pregnancy,’ He replied

The gene Dr He edited is called CCR5 and is involved in regulating the body’s immune system. 

Although naturally-occurring mutations in CCR5 have been associated with higher levels of resistance to infection specifically in European populations, these do not block all strains of HIV. 

He sought to disable a gene called CCR5 that forms a protein doorway that allows HIV, the virus that causes AIDS, to enter a cell.

All of the men in the project had HIV and all of the women did not, but the gene editing was not aimed at preventing the small risk of transmission, Dr He said.

Dr He also failed to present a long-term plan to monitor the two children in order to assess the knock-on impact of the procedure, experts say. 

Pictured: An embryologist who was part of the team working with scientist He Jiankui adjusts a microplate containing embryos at a lab in Shenzhen in southern China's Guandong province

Pictured: An embryologist who was part of the team working with scientist He Jiankui adjusts a microplate containing embryos at a lab in Shenzhen in southern China’s Guandong province

This graphic reveals how, theoretically, an embryo could be 'edited' using the powerful tool Crispr-Cas9 to defend humans against HIV infection

This graphic reveals how, theoretically, an embryo could be ‘edited’ using the powerful tool Crispr-Cas9 to defend humans against HIV infection

WHAT IS CRISPR-CAS9?

CRISPR-Cas9 is a tool for making precise edits in DNA, discovered in bacteria.

The acronym stands for ‘Clustered Regularly Inter-Spaced Palindromic Repeats’.

The technique involves a DNA cutting enzyme and a small tag which tells the enzyme where to cut.

The CRISPR/Cas9 technique uses tags which identify the location of the mutation, and an enzyme, which acts as tiny scissors, to cut DNA in a precise place, allowing small portions of a gene to be removed

The CRISPR/Cas9 technique uses tags which identify the location of the mutation, and an enzyme, which acts as tiny scissors, to cut DNA in a precise place, allowing small portions of a gene to be removed

By editing this tag, scientists are able to target the enzyme to specific regions of DNA and make precise cuts, wherever they like.

It has been used to ‘silence’ genes – effectively switching them off.

When cellular machinery repairs the DNA break, it removes a small snip of DNA.

In this way, researchers can precisely turn off specific genes in the genome.

The approach has been used previously to edit the HBB gene responsible for a condition called β-thalassaemia. 

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