Extracts from the controversial scientific paper penned by disgraced Chinese biophysicist He Jiankui have been revealed for the first time.
A full-length piece of research has never before been published or verified, but excerpts have now been obtained and published by MIT Technology Review.
The abstract of the alleged paper, which is littered with oversights, errors and ethical neglect, compounds concerns over the project which may have created unintended mutations.
Experts who reviewed the extracts have called it ‘delusional’, ‘outrageous’ and ‘preposterous’.
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Extracts from the controversial scientific paper penned by disgraced Chinese biophysicist He Jiankui have been revealed for the first time.
He, along with nine listed co-authors, proclaims his work as a ‘success’ and goes as far as to say it ‘will bring new hope to millions of families seeking healthy babies free from inherited or acquired life-threatening diseases.’
Fyodor Urnov, a genome-editing scientist at the University of California, Berkeley, told MIT Technology Review that this was a ‘deliberate falsehood’.
Professor Urnov added: ‘The statement that embryo editing will help millions is equal parts delusional and outrageous, and is akin to saying that the 1969 moonwalk ‘brings hopes to millions of human beings seeking to live on the moon.”
Dr He stunned the world when he announced the use of gene-editing technology CRISPR-Cas9 to alter the embryonic genes of twin girls, nicknamed ‘Lulu’ and ‘Nana’.
The disgraced researcher’s justification for the experiment was to confer HIV immunity to the embryos in later life.
Many reports claimed this was due to the father being HIV-positive. This is false, as the father’s HIV status was neutralised using a long-established technique called sperm washing.
Being HIV positive carries a significant social stigma in China and makes it almost impossible to have access to fertility treatment.
Sperm washing prevents the infection from being passed on to unborn children but can often result in exclusion from fertility treatment.
By targeting HIV-positive families, He may have motivated the parents to take part in the experiment despite the huge risks to their children, Jeanne O’Brien, a reproductive endocrinologist at Shady Grove Fertility told the MIT Technology Review.
Instead of the traditional route of publishing research in a respected journal where it can be scrutinised and dissected following repeated denial, including from prestigious journals Nature and JAMA, Dr He announced his heinous work to the world via YouTube.
It caused international outrage in November 2018 when academics and members of the public became aware of the extent of the ethical violations.
The gene Dr He intended to edit is called CCR5, and it 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 CCR5, to stop it forming a protein doorway that allows HIV, the virus that causes AIDS, to enter a cell.
While the team targeted the right gene, they did not replicate the ‘Delta 32’ variation required, instead creating novel edits whose effects aren’t clear.
This was viewed as the sole goal for the research, but Professor Urnov says ‘there is zero evidence in the manuscript supporting the essential expectation that the new forms of CCR5 would be HIV-protective’.
The gene Dr He intended to edit is called CCR5, and it is involved in regulating the body’s immune system. He sought to disable CCR5, to stop it forming a protein doorway that allows HIV, the virus that causes AIDS, to enter a cell
The legitimacy, not to mention the safety implications, of this research led to universal condemnation. The conspicuous absence of a peer-reviewed paper exasperated these problems.
In what appears to be a non-peer-reviewed proof seen for the first time, researchers pick apart the reasoning, methodology and morality of the procedure.
One simple and major cause for concern unearthed by the extract is a stunning lack of collaborators on the project. An undertaking of this magnitude would be expected to have dozens of collaborators.
Only ten authors are named, with no doctors or obstetricians listed, which indicates the medical professionals helping to conduct the IVF and birthing were unaware of the ethical violations that had taken place.
This is thought to be part of a cover-up to make it difficult to identify the family and the twin girls.
By removing the names of doctors and including a false date of birth, it makes it nearly impossible to track them down with such little information available.
One of the authors listed is one Michael Deem, of Rice University in Texas.
Dr Deem was He’s former adviser, physics and bioengineering professor and Rice University investigated the role he played in the experiment.
In the paper, He seeks desperately for validation of his barbaric experiment, which unnecessarily endangers the lives of two twin baby girls in order to confer HIV protection.
To this end, He states that gene-editing could be used to help cure and prevent future HIV infection and improve upon existing medicine and treatments.
Rita Vassena, scientific director, Eugin Group, dismisses this notion as ‘an attempt to find a defensible reason to use CRISPR/Cas9 technology in human embryos at all costs’.
Dr Vassena adds: ‘The idea that editing-derived embryos may one day be able to ‘control the HIV epidemic,’ as the authors claim, is preposterous.
‘Public health initiatives, education, and widespread access to antiviral drugs have been shown to control the HIV epidemic.’
A singular paragraph is dedicated to one of the largest issues facing the use of gene-editing on human embryos, unintentional mutations introduced via CRISPR, known as unwanted edits, called ‘off-target’ mutations.
He writes: ‘Off-target effects and large-scale deletions are major safety concerns for CRISPR genome editing’.
This, it seems, may be one of the few indubitable statements in his paper.
But then he continues: ‘After thoroughly assessing all treated embryos for off-targets and large deletions by whole genome single cell sequencing, one edited embryo did not show any off-target mutations.
‘The other embryo showed one possible off target…we concluded that this off-target genomic insertion might not impact any biological function.’
Professor Urnov said: ‘An egregious misrepresentation of the actual data that can, again, only be described as a blatant falsehood.
‘It is technically impossible to determine whether an edited embryo ‘did not show any off-target mutations’ without destroying that embryo by inspecting every one of its cells.
‘This is a key problem for the entirety of the embryo-editing field, one that the authors sweep under the rug here.’
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
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.
