Gene therapy, considered by many to be the holy grail of medicine, involves editing disease-causing mutations out of genes to prevent diseases. CRISPR is a new way to edit genes that has been used to stop mice from developing many different diseases including muscular dystrophy, liver disease and cataracts. It has also been used to treat human cells collected from patients and grown in the lab.
CRISPR had not, until very recently, been used in humans or human embryos because we still don’t know whether this treatment is safe. Last month a group of scientists from China announced that they had used CRISPR in human embryos. This created an uproar because many people believe it is unethical to alter genes in human embryos. There is a fear that this sort of technology could eventually lead to ‘designer babies’ where parents could order from a catalogue of desirable traits. However, many other people believe that gene editing should be used to prevent babies from being born with incurable genetic diseases like cystic fibrosis.
In an attempt to side-step the ethical issues, the Chinese scientists used 86 non-viable embryos from a fertility clinic. During IVF, these embryos had been fertilised by two sperm instead of one and so would not be able to develop into live babies. The scientists used CRISPR to edit the human β-globin (HBB) gene in these embryos. Mutations in the HBB gene cause the blood disease β-thalassaemia. The scientists injected the CRISPR ingredients into the embryos when they were still single-cells so that if the HBB gene was successfully altered, the edits would be in every cell as the embryos divided and developed. They then waited 48 hours until the embryos had divided into eight cells and checked whether the gene editing had been successful.
They found a number of problems which showed that the CRISPR technology is not yet ready to use in human patients. Many of the studies using CRISPR in mice or in human cells grown in the lab showed that CRISPR is very efficient in editing out gene mutations. However, this was not the case in the human embryos. Out of 86 embryos injected with CRISPR only four were successfully edited – that’s less than 5%.
CRISPR works by cutting DNA around a mutation and then using a DNA template to repair the cut DNA so that the gene now has a normal sequence. During CRISPR treatment, the correct DNA template is injected into cells along with the enzymes needed to cut and repair DNA. The Chinese scientists found that in seven of the human embryos they treated, the CRISPR system used another gene called the delta-globin gene instead of the injected DNA template to repair the HBB gene. Until we fully understand why this happens in some cases, we cannot use CRISPR to treat humans as we cannot tell exactly how we will re-write the treated genes.
Another problem was that CRISPR treatment caused a lot more unintended mutations in the human embryos that is usually seen in mice or lab-grown cells treated with CRISPR.
Until we ensure that CRISPR can efficiently treat only the targeted mutation, and not cause other mutations, it remains unequivocally unethical to use it in humans.
The Scientific Paper (free and open access):