Birth of first genetically edited babies
Designer babies are now a reality
When it comes to the news in genetics, very few blockbuster headlines come out that can be compared to the degree of what was announced this week from China: researchers declared the birth of the first human baby that was genetically modified prior to birth. We are ushering in the era of designer babies. It was not that long ago that we discussed this topic as a too distant possibility to merit serious discussion. Indeed, not that long ago it was not. It is incredible that in a mere few years, China has made such leaps in the use of genome editing technologies to start experiments on human subjects.
However, for the moment, while world’s condemnation continues to pour in, the validity of these claims are yet to be independently confirmed.
But let’s start from the beginning of the human genome editing odyssey, as this is not new and not the first time it was to be demonstrated.
Brief history of tinkering with the code of life
First let’s define the technology in question, as human genome editing has actually been going on for decades already. Specifically we are talking about using the famous CRISPR/Cas9 that has progressively been enhanced, in its accuracy since its discovery just a few years ago. What differentiates CRIPR/Cas9 is that it allows targeting to an exact desired location in the genome for editing to take place. Prior technologies relied on the random insertion of new genetic material into the DNA without much regard as to where this incorporation into the genome would take place, or the fact that original faulty DNA information would still remain in the genome. So CRISPR/Cas9 presents huge advantages towards controlled human genome modification.
Next, let’s define what type of human genome modification we are talking about: post birth or prior to birth in the early stages of development. The distinction here is that genome editing prior to development will mean that such edited genomes will also be present in the reproductive cells of the individual, and hence can be potentially be passed on to future generations. Currently such editing is regarded as unsafe and banned by scientific societies around the globe precisely because we just don’t know enough about long-term safety as related to genome editing.
Human genome modification at a designated location in adults had already commenced in 2017 in an attempt to help people afflicted with Hunter syndrome. And even that we have to further define, as modification was taking place directly inside the body of these patients. Targeted human genome editing in tissues that were subsequently introduced back into patients has also taken place previously. One such example was genetically modified skin to help treat a devastating skin condition in a young boy. An even earlier demonstration was the modification of immune cells to prevent infection with HIV, and we will definitely be coming to this topic right away.
In the meantime, the first demonstration of human genome editing in fertilized eggs (zygotes), was already broadcasted in 2015, also in China. The goal was to remove a genetic mutation that was a precursor to beta-thalassemia, a type of blood disorder. While this was executed in non-viable embryos that had extra chromosomes (due to the fertilization of the egg with two sperms), at the time even this drew worldwide condemnation. If anything, it proved to the world that the technology of editing human genomes was not ready, as the editing was incomplete so some of the cells in the subsequent embryo were edited and some were not. On top of that, some editing took place where it was not supposed to.
Yet China must really want to be a leader in this field, as in 2016 the second demonstration of genome editing in human zygotes took place. This time it was to introduce a mutation in a CCR5 gene in order to establish resistance to the HIV virus infection. In comparison to the first such announcement a year prior, the second time around no one seemed to notice, or no one seemed to care. The reaction was muted. Been there, done that - just another tampering with a human genome in an embryo. And just like before, the authors of this second attempt noted that “significant technical issues remain to be addressed” when it comes to use of CRISPR/Cas9 technology in human embryos.
Modified genome baby – what has been done?
Perhaps this helped to encourage the Chinese scientists towards the latest step of actually engineering the genome of an embryo that would eventually result in a live birth. And for whatever reason, the prior reports on the limited success rate of the editing technology did not seem to discourage them. But the announcement of this still yet unconfirmed event has drawn worldwide criticism, approaching outright condemnation.
The leader of the research team, and the person who made the announcement, was Dr. Jiankui He, and he certainly has guaranteed himself a place in history no doubt. Judging how much disapproval he is currently facing, only time will tell if history will be a kind or severe judge. The claim was made on November 25, 2018 in Hong Kong to one of the organizers of an international conference on gene editing, and also in an exclusive interview with the Associated Press, which broke story on the edited genome babies.
So what are the claims?
He apparently helped to produce the first people born with edited genomes, seemingly born earlier this month. They were twin baby girls of Chinese parents, including a father that is infected with the HIV virus. The fertilization was an in vitro fertilization using donated parental sperm and eggs, and the zygote was apparently injected with CRISPR/Cas9 to allow for the direct editing of the CCR5 gene, the same gene that was targeted in the 2016 experiments in un-viable zygotes. The functional copy of this gene is required for HIV to infect immune cells, and people with a deleted copy of this gene are known to be resistant to HIV infection. The justification for this procedure apparently was on the grounds that people with HIV still face extreme discrimination in China and other parts of the world, and the parents did not wish to risk such a fate for their children.
That in itself sounds dubious, but there are a handful of other serious issues for which this scientist drew so much criticism.
First of all, this came out of nowhere! He had never before presented his work publicly, and announced his landmark project in a YouTube video! There was a lack of transparency and oversight that is deemed improper for such an important work involving the experimentation on human subjects.
The choice of the gene has also been questioned as an inappropriate justification to experiment with human life, on otherwise normal healthy embryos. While it is known that mutations in this gene can confer resistance to HIV infection, the full function of the gene in humans is not even known! There are also other well-established methods to prevent contracting HIV, thus completely negating the need of this procedure. It is already known that people without normal CCR5 genes face higher risks of being infected by other viruses that can be quite dangerous. Thus this was deemed an inappropriate target for such an important experiment, and in fact potentially putting people in harm’s way!
On top of that, in one of the twins, both copies of the CCR5 gene were successfully mutated, conferring the future resistance to HIV. But in the other twin, only one copy of the gene was successfully mutated, meaning there are no benefits to that person at all. What is shocking is that the researchers knew that and still chose to proceed with the implantation of the embryo in the mother. No one can fully grasp why this happened as it is totally unjustifiable.
Dubious start, dubious future of genetically modified humans
Time will tell if this experimenting with humans will be beneficial to subjects or actually harm them. There are other potential harms besides the biological impact. These children will obviously be scrutinized in detail from both a scientific point of view, as well as having the world’s attention on them, likely for the rest of their lives. The scientific attention might perhaps be beneficial as these children will likely receive the best clinical care the world will be able to offer in the process of studying their health, but the type of media attention might certainly not be welcome, and these girls did not have an option of refusal.
As for the accuracy of the technology, apparently it worked perfectly, without off-target editing that could be detected with genome sequencing. Perhaps there was one, but it was deemed harmless. Others questioned the validity of this as well, in that the confirmation process was not rigorous enough.
It gets worse!
The hospital claimed to have given the ethical approval for this experimental work has denied it, claims that the medical-ethics committee to overview this research never actually took place, and suspected the authenticity of the signatures on the clinical trial approval form for the CCR5 gene modification in human embryos.
The University where this scientist works also claims it was never aware of his work. The University released a statement, that included a call for “international experts to form an independent committee to investigate this incident, and to release the results to the public”.
In the meantime, this work has also been condemned by some of the highest scientific societies in China, and the entire murky circumstances are under investigation, including by a local government.
Rapidly the Chinese authorities are also distancing themselves from this event, historic or not.
So what does it mean moving forward? Will we see the repeat of what has happened with the genetic modification of human zygotes? Incredible condemnation of the first ever event, followed by indifference with the next experiment? It seems doubtful, as the reaction this time is too severe, and some even worry this might impede proper research in this area. And certainly research should continue as we are talking of a potential to cure genetic diseases. But there are reasons why the world currently prohibits this type of experimentation on human beings, precisely because so much more research needs to be performed.
But could this also mean that now that the gene-genie is out of the bottle, and now that the first precedent has been set, that we going to see a wave of human genome editing? I don’t think we will see a tsunami, but would venture a guess that yes, there now will be other examples, justified by presumed medical need, although likely following more stringent criteria than was exercised in this first example. And wait till we start injecting DNA code that is non-human, also likely sold to the public under the need of improving human health. How soon will it be before we hear of the first human GMO? This truly likely ushers in a new era for humanity that will test our collective concept of ethics.
After all, apparently there is still one more pregnancy involved with a genetically edited baby on its way from the same team of researchers.
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