EXPERT REACTION: Reports of first genome edited babies
Organisation/s: The University of Sydney, South Australian Health and Medical Research Institute (SAHMRI), The University of New South Wales, Murdoch Children's Research Institute (MCRI), The Australian National University, , Queensland University of Technology
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
The report of successful genome editing, dubbed ‘gene surgery’ by the Chinese scientist who supervised the work, is long on controversy but short on detail. Technologically, the procedure is the same as the one I and many others routinely use in mice to change the sequence of DNA. Scientifically, the main questions regarding the gene edited babies are what changes other than those intended might have been generated (it’s almost impossible to say for sure), and whether altering a gene involved in HIV infection might have other, unexpected physiological or medical consequences.
With mice, we can arguably afford to take some risks in the face of many unknowns. But the gene-edited human twins are not lab animals, and it’s no wonder the work has resulted in a storm of ethical controversy. The twins had no specific disease, and the treatment is instead supposed to lower the possibility of HIV infection – some may say a designer trait – the two situations are ethically poles apart.
Most importantly, the genetic change will be passed on to all future generations in that family – not only any potential benefits but also any potential problems. This is why most of the world has the brakes on CRISPR gene therapy until we can fully assess the risks and benefits. For some, the temptation to bypass international safeguards and be the first to plunge into the unknown is always going to prove too great, as may be the case here.
Unusual, unsafe, unverifiable, unethical and dangerous I think.
Unusual because ethics approval appears superficial and to have been granted after the fact, and the procedures appear to have been conducted by a company at an undisclosed location under the misleading banner of “vaccine research”.
Unsafe because investigations into the off target effects of the gene correction procedure appear incomplete and insufficient, and adverse effects later in life cannot be excluded at this stage.
Unverifiable because the data have not been submitted to peer review scrutiny.
Unethical because the correction itself does not actually prevent a genetic disease but rather protects against HIV infection, which itself is readily preventable. Furthermore it appears that even embryos that were known to have uncorrected genomes were allowed to proceed, suggesting the focus was not on health outcomes, but rather the procedure itself.
Dangerous because for good reasons (ethical, scientific and philosophical ones) the wider scientific community has agreed on a ban on human germline (heritable) genome engineering until it can be proven to be safe, and appropriate guidelines are agreed upon.
Conducting human germline experimentation in this fashion is unacceptable and could create a back lash that sets the field of genetic medicine back many years.
Gene editing has great potential, but all research operates under a social licence and experiments that risk undermining this licence are detrimental to the entire field. Through the science engagement activities we are running in Australia, we know the majority of people are open to using gene editing in humans but only provided it is performed to cure a disease and that the risks are well understood. Editing human embryos would impact several generations and the long-term effects are still unclear. At this stage, the risks would still outweigh any potential benefit. Such experiments should not take place until there is an international consensus that it is safe enough to do so.
While we await independent verification of these claims, we stress that human germline modification is a delicate area of research that must conform to stringent legal and ethical guidelines. Any such intervention must be bound by a serious, unmet medical need in the absence of an alternative medical approach.
Chinese researcher He Jiankui of Shenzhen claims to have gene edited two healthy embryos, resulting in the birth of baby girls born this month, Lulu and Nana. He edited a gene to make the babies resistant to HIV. One girl has both copies of the gene modified while the other has only one (making her still susceptible to HIV).
If true, this experiment is monstrous. The embryos were healthy. No known diseases. Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer. There are many effective ways to prevent HIV in healthy individuals: for example, protected sex. And there are effective treatments if one does contract it.
This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit.
It contravenes decades on ethical consensus and guidelines on the protection of human participants in research.
In many other places in the world, this would be illegal and punishable by imprisonment.
Could gene editing ever be ethical? If the science progressed in the future and off target mutations reduced to acceptable and accurately measurable levels, it might be reasonable to consider first-in-human trials (with appropriate safeguards and thorough ethics review) in one category of embryos: those with otherwise lethal catastrophic genetic mutations who are certain to die. Gene editing for this group might be life-saving; for these current babies, it is only life-risking.
These healthy babies are being used as genetic guinea pigs. This is genetic Russian roulette.
Today the news outlets are reporting the generation of the first gene edited babies from researchers at Shentzen in China. The reports indicate the birth of twins carrying mutations in a gene giving a protective effect against HIV infection.
Given the lack of details in these reports, it would be wise to take this information with a lot of caution. While gene editing technology undoubtedly has a potential to cure diseases, there is still a lot we don't know about long term effects or unintended consequences as one of the twins carries mosaic alleles [Ed - cells with different genomes in one individual]. There are also a series of concerns about how this study was performed such as whether the parents were fully aware of the risks and benefits, or the fact that some health workers were unaware of this work being carried out.
While gene editing embryos is not allowed in Australia, this report raises many concerns around how this study was performed, and the lack of proper institutional ethics approval. Overall editing human babies is to date too premature and requires a broad discussion with stakeholders on the future of human embryo editing.
If true, the recent reports of the first genetically edited human babies are completely irresponsible and for no direct or immediate benefit to the babies edited or human kind. In fact, we don’t know the full impact of targeting the CCR5 gene in various human genetic backgrounds, and there is no urgent need to discover this at the potential expense of a newborn innocent child. Moreover, we have no idea what side effects the editing process may cause.
If the goal is to help eradicate HIV, we can edit the CCR5 gene in the bone marrow of infected patients and then transplant these HIV resistant cells back into the infected patient. There is considerable evidence that this will ‘cure’ HIV in these patients.
Less than 1 percent of the world’s population has HIV, however by disrupting the CCR5 gene in a healthy human, they will likely become more sensitive to a variety of much more common infections, and something relatively benign like the flu may now be lethal.
Before we start editing human embryos to try and control disease, we first need to better understand the safety issues involved, and importantly we need to identify the most appropriate disease to target, in this case prophylactic editing to control future HIV infection was not justified.
In the end the motivation here seems to be one of personal glory for the scientists involved, and there may be a horrific cost to pay for this hubris.
Important to note that at this stage the reports have not been independently verified so it’s hard to say if the claims are real. Scientists everywhere today will be thinking “show me the evidence” and some of the claims from the scientists involved suggest that the gene editing was only partially successful. If confirmed, this represents a huge technological and ethical leap. It’s possible we just saw a huge leap towards editing the human book of life - some might even suggest this is a step towards eugenics.
Even seeing the detailed data may be tricky. No reputable scientific journal should touch this story if the experiment was done without the appropriate ethical approval (as seems likely from comments attributed to the scientists involved). This aspect of the story is really problematic and disturbing. Experiments like this risk setting back the entire field. Science operates under a social licence - scientists work within limits defined by broader community concerns. Ignoring those boundaries risks a justified backlash and fear that can set back the entire field by decades.
Most scientists think that the safety concerns around gene-editing in humans are still too big to outweigh any potential benefit. We don’t know the long-term effects of CRISPR editing in humans. There are significant safety concerns are around the possibility of “off target” gene edits (ie editing unintended genes) and the tendency for editing to work most efficiently in cells where a major tumour suppressor gene (p53) is silenced.
While completely unsubstantiated, the reports today of the birth of the first genome-edited babies (twin girls) are hugely alarming.
The field of gene-editing is advancing rapidly, but isn’t without concern. For each research story of hope, another is published providing evidence of off-target effects, and large deletions incorporated at the cut site, all of which suggest that research needs to proceed cautiously. CRISPR-based gene editing is very much still in the experimental stage, particularly in human embryos, where the most recent research questions the success rates and efficacy of the technology.
The story in today’s media, which describes couples who were offered free fertility (IVF) treatment in return for experimental gene editing of their embryos seems immoral. Rather than the proposition of fixing a DNA error which could not be avoided in the next generation, the reports suggest that the gene that was edited provides resistance to HIV infection. To edit a gene unnecessarily, for which there are evidence-based, safe and affordable solutions (protected sex) is irresponsible and dangerous.
Other points of major concern in the report include:
- The conflict of interest of the “researchers” who own companies/have a financial interest in the success of the technology.
- The report that the lab didn’t know they were dealing with patient samples that were HIV positive (reported to protect the status of the patients involved).
- The reports that the “researchers” involved have no experience running clinical trials, and who are trained in physical sciences.
- The report that the patients may not have been appropriately briefed on the experimental nature of the trials.
- The report that an embryo with a known failure in the editing process was transferred, suggesting that they were actually interested in testing the safety/efficacy of the technology and not the genetic resistance to HIV for the patients/babies.
It is important to recognise that these reports remain unsubstantiated, but are of grave concern. The implications for cowboy-style “researchers” taking experiments into their own hands risk damaging the already fragile relationship between science and society.
While this research has yet to be subject to peer scrutiny (which in itself is problematic), it looks like the researcher involved wanted to be the first rather than waiting to be safe. It is still early days for human genome editing; with lots of scientific and ethical issues needing to be ironed out before it is used to change a genome of an embryo and its future descendants.
Susceptibility to HIV infection is not an obvious target for genome editing. We don’t need genome editing to prevent HIV - we need to make existing preventive measures and treatments more widely available. Editing the DNA of healthy embryos to reduce the risk of contracting HIV is neither necessary nor appropriate.
This announcement also risks undermining the very careful research being undertaken globally to investigate the safety and future potential uses of genome editing to help avoid children being born with severe, life-limiting diseases.
If it is shown that these twin girls have indeed had their genomes edited, I hope that they are supported both medically and socially as they grow up; without becoming public curiosities.
Every position statement that I’ve seen globally has condemned the editing of human embryos for reproductive use at this point in time. What seems to have happened would be illegal in Australia and carries a criminal penalty here,
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