GM humans are possible, but do we really want them?
We are entering a new era as a species. For the first time, we are not only able to read our genetic code but also edit it. This will revolutionise our ability to treat disease and it will improve the lives of millions if not billions of people. But it means that, if we want to, we can now edit human embryos to “improve” the characteristics of our children. We will be able to create designer babies and these changes will be passed on to their descendants, which will change the human species forever.
It is worth thinking about the scale of what we can now do. The human genome is made up of 3 billion characters, which is about ten times the size of Encyclopaedia Britannica. This contains all the information needed to make a human, and it determines nearly all our characteristics as individuals (not only height, athletic performance and IQ but also our personality and even political views). We completed the first sequence of the human genome around 20 years ago at a cost of US$2.7 billion. We can now sequence a genome for less than the cost of an MRI scan.
In the past decade, there has been an explosion in the technology that allows the genome to be edited. This means that we can change the letters of the genome at nearly any site we choose. This is an incredible feat. It is like being able to walk up to a shelf in a library, select the correct volume, page, line and word and then change only a single character. Amazingly, this can be done in billions of cells at the same time. It is also possible to edit cells inside living animals using viruses to make the genetic changes.
Genome editing will be a huge power for good. It means that we can fix broken genes directly. This will allow debilitating genetic disorders, such as sickle cell disease and muscular dystrophy, to be cured. We will also be able to use this technology to reprogram cells to kill cancerous cells and perhaps even modify organs to reduce cholesterol levels. This can probably be done with few ethical problems by modifying cells of specific tissues.
Changing the germline
By contrast, editing the genome of human embryos is hugely problematic. Editing the embryo when it is a single cell causes genetic changes to occur in every cell in the baby’s body, including their reproductive organs. This means that the changes will not only be made to the baby but all their descendants.
Scientists have found that it is remarkably straightforward to edit mammalian embryos using IVF technology to inject tiny quantities of editing molecules. This has been optimised to generate thousands of genetically modified laboratory animals, which has led to rapid advances in our understanding of many biological processes and disease models. Yet the same technology can be used to edit human embryos, which are very similar to other mammalian embryos.
The main reasons people are likely to edit human embryos is for augmentation, such as improving intelligence or height. It is unlikely to prove that useful for treating genetic disease because nearly all severe genetic disorders can be prevented by pre-implantation genetic diagnosis. Here the embryo is tested to check if it has a mutation before it is put back into the uterus.
The only time pre-implantation diagnosis won’t work is the very rare instance when both parents have the same recessive genetic condition when there is a 100% chance the baby will be affected. But it would still only be justifiable to do germline editing if the disorder is not treatable in another way, such as gene editing of the affected organs.
In 2018, the Chinese scientist He Jiankui edited human embryos try to make babies resistant to HIV. This led to an outcry in part because it is not possible to ensure the safety of editing human embryos at present and the risks could not be justified because transmission of HIV from mother to baby is very rare with proper medical intervention.
Despite this, Russian scientist Denis Rebrikov now appears determined to do germline genome editing. This also seems to be a vanity project rather than being in the best interests of the parents or children involved. But it is interesting because it demonstrates how difficult it is to find cases where it is possible to even tenuously justify germline editing; paradoxically helping the argument that it should be outlawed.
Rebrikov has managed to track down five couples where both parents have the same genetic mutation causing deafness. But this mutation does not always cause severe deafness – it can only cause mild hearing loss and this is not predictable in advance. Importantly, severe cases are readily treatable with cochlear implants, which are effective.
The edit needed to fix this defect is not straightforward. He will have to discard at least half of the embryos he tries to edit. And there is a risk he will cause unintended mutations that will not be detectable until after the children are born.
Some people argue that genome editing embryos is ethically justifiable because it means you don’t have to discard embryos, unlike pre-implantation genetic diagnosis. But cells that can create viable humans will always have to be destroyed to test that the edit has been successful.
If we develop technology for editing human embryos, it is likely to lead to widespread human augmentation. Many of the genetic sequences associated with intelligence and athletic performance are already known and recent advances in editing technology mean that it will soon be possible to make hundreds of precise changes at the same time. This raises the possibility that, in the future, parents will be able to choose to have sets of edits to improve IQ, athletic performance and appearance, simultaneously.
If it is taken up by large numbers of people, it is likely people will feel obliged to have their offspring genetically augmented to give them a good chance in life. Unscrupulous governments are also likely to use this technology to generate elite athletes if doping programmes of the past are anything to go by, and it isn’t too difficult to see the potential advantages of genetically engineered soldiers.
It is important that, as a society, we understand the potential ramifications of allowing editing of human embryos and that we do not use this technology indiscriminately.
James Davies is funded by the Medical Research Council and is a Co-founder of Nucleome Therapeutics.