QUANTUM LEAP

Techniques based on CRISPR CAS9 gene editing are to be done with unprecedented precision. CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, are naturally occurring repetitive sequences of genetic code, which are part of the immune system.

When an alien bacteria or virus invades the body, CRISPR is “programmed” to recognise the alien material. It then uses CAS-9 — an enzyme produced by the CRISPR system — to bond with the alien DNA and excise it. It does this cutting in a precise fashion. New DNA can be inserted to replace the excised material. If no new DNA is inserted, the DNA repairs itself, joining up the cut ends. CRISPR can be programmed to recognise multiple genes simultaneously as well. Apart from being used as a gene-editing tool, CRISPR CAS9 can also function as a diagnostic tool. It can recognise target DNA very quickly and identify viruses such as zika and dengue very efficiently.

One fantastic implication is that gene editing causes a permanent change. The edited organism will pass on changes to its descendants. One worry: As edited DNA repairs itself, it can result in unforeseen mutations with dangerous consequences.

There have been multiple experiments using CRISPR. Crop editing is common, for example. Scientists have removed the muscular dystrophy gene and cured Huntington’s disease — a nervous disorder of brain cells — in mice using CRISPR. Experiments with pigs suggest that CRISPR could help grow organs for human transplants in cloned pigs, removing porcine genes that may harm humans.

The Bill & Melinda Gates Foundation has invested in research that seeks to eradicate malaria by preventing the malaria parasite from developing. It may even be possible to breed the Aedes aegypti mosquito (carrier of zika and dengue) into extinction by encoding a “male only” instruction so that only male mosquitoes are born. Some experiments suggest cancer genes can be targeted. Strange experiments have also been carried out — for example, scientists successfully removed the gene that carried olfaction (sense of smell) — in ants.

Obviously, this is a massively powerful technique and has huge moral and ethical implications. The temptation to rush headlong into editing human genes is strong. Diabetes, cancer, Parkinson’s, susceptibility to heart disease, etc are known to be caused by specific genes; the diseases could be eradicated if those genes could be safely removed. However, the dangers of research involving humans is high and most nations have laws to prevent such research from being conducted in an irresponsible fashion.

In 2015, some dangers became apparent. Researchers led by Junjiu Huang at Sun Yat-sen University in Guangzhou, used “non-viable” embryos, (which cannot result in a live birth) in a study. The team modified the gene responsible for ßthalassaemia, a potentially fatal blood disorder. The study showed serious issues.

The Chinese team injected 86 nonviable embryos with CRISPR programmed to remove the gene mutation responsible for ß-thalassaemia. Of these, 71 embryos survived and 54 were genetically tested. Just 28 embryos were successfully spliced. There were also many unexpected mutations.

However, a 2017 study, titled “Correction of a pathogenic gene mutation in human embryos” ( https://www.nature.com/nature/journal /vaop/ncurrent/full/nature23305.html) may have successfully tackled some issues. An American team led by Shoukhrat Mitalipov of Oregon Health & Science University managed to correct a mutation in the gene MYBPC3, in viable human embryos. This mutation is believed responsible for about 40 per cent of the heart disease, hypertrophic cardiomyopathy. An individual only needs to inherit one abnormal copy of the gene to be affected. An individual carrying the gene will pass it on, about half the time.

The researchers used sperm from a patient carrying one copy of the MYBPC3 mutation to create 54 viable embryos. They edited these using CRISPR-Cas9. In the first round, 36 out of 54 embryos were normal. Of the remaining 18 embryos, five were unchanged and in 13, only some cells had been edited.

The researchers tweaked the experiment, injecting sperm and the CRISPRCas9 complex into the egg at the same time. This was done for 75 mature donated human eggs. This time 72.4 per cent of embryos were normal. Embryos containing unedited cells (“mosiacs”) reduced. Unexpected mutations were low.

This is indeed promising. But it didn’t work 100 per cent, which is the ideal. Further research is obviously required. The ethical debate will also need to be updated to take this study into account.