Gene editing: CRISPR raises many questions about risks and ethics

The idea of eliminating and inserting genes throws up immense possibilities, but it also raises many questions about risks and ethics

Last October, bioscientist and former NASA researcher, Josiah Zayner tried a path-breaking experiment with himself as the subject. 

Zayner switched on his video camera, invited a few scientists to act as witnesses and edited his own genes. He live-blogged this with a running commentary.

Zayner used a new technology, called CRISPR, to remove the myostatin gene from the cells on his forearm. Myostatin inhibits the growth of muscle. If the experiment works, Zayner should eventually end up having bigger muscles on one forearm

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But more than the success or failure of this experiment, Zayner was simply demonstrating that genetic hacking (bio-hacking is what it’s being called) was possible. He also handed out small bags of the DNA he used, explaining that it took him little time to prepare.

The CRISPR-Cas9 process is a discovery that has, within a few years, transformed genetic editing. It is literally a cut-and-paste tool.

CRISPR can target a specific gene in somebody’s DNA and excise that gene, and if necessary, replace it with something else. I’m simplifying the explanation but the mechanics are really not very complicated. 

The choice of gene for excisions, and insertion, is very complicated, of course.

CRISPR, which stands for Clustered Regularly Interspaced Palindromic Repeats, allows do-it-yourself gene editing. It uses a defence mechanism that evolved naturally. 

In 2008, food scientist Rodolphe Barrangou was examining the bacteria in curd and he discovered that Streptococcus thermophiles, the bacteria that transforms lactose into lactic acid, had repetitive sequences. Those sequence seemed to be able to combat the bacteria and viruses that spoil yoghurt. 

DuPont took over Barrangou’s company and started using these naturally occurring CRISPRs to protect cheese and yoghurt from spoilage. Scientists also discovered that CRISPRs existed in many genomes.

In 2012, biochemist Jennifer Doudna and microbiologist Emmanuelle Charpentier discovered the Cas9 mechanism. 

Cas9 is an endonuclease — an enzyme that splits DNA chains into two or more chains. Cas9 works on a “find-replace” principle: it recognises specific DNA sequences that it can then remove, and it has developed as an immunisation system.

In nature, CRISPR-Cas9 recognises and removes viruses that the body recognises as dangerous. But it can be trained to recognise, and replace, all sorts of DNA sequences.

This form of exact genetic editing opens up huge vistas. Six months after Doudna-Charpentier published their findings, another molecular biologist, Feng Zhang, published a paper that demonstrated how CRISPR-Cas9 could edit human cells. 

The three pioneers and their associates then took out patents, and those patents are still under dispute. However, between them, they also floated several CRISPR-editing companies and these entities are now starting to trial-edit human DNA.

Genetic editing of this nature is the promised land in terms of what it can possibly do to cure disease, and change and enhance human abilities. 

It is also an ethical minefield because it can do a lot of things that make any thinking person a little uncomfortable.

It’s useful to understand that CRISPR is already extensively used to engineer plant genetics, and animal genetics too. We've already mentioned dairy products. 

This technique is also used to modify crops like maize, corn, potato, soybean, wheat, and so on. Gene editing can be done to inhibit spoilage, increase yields, reduce water dependency, resist diseases et cetera.

This technology has also been successfully applied to genetically-modify rabbits, swine, goats, sheep and cattle. 

Apart from breeding specific qualities into these animals, it is possible to do weird trans-species things like breed goats that produce spider silk in their milk. It may even be possible to culture human organs, such as kidneys, in pigs for the purpose of transplants. 

In many cases, CRISPR-Cas9 can be used to quickly induce changes that could have occurred through natural breeding methods over generations. 

For example, strawberries or mangoes can be bred to increase sweetness. In such instances, there isn’t much paperwork required. Trans-species editing, taking a gene from one species and popping it into another, requires extensive clearances.

But what of using CRISPR on humans? Zayner has started handing out DIY kits for demonstration purposes. 

While most nations have laws against editing human DNA, the technology is easily accessible. So, it is likely to happen. 

Editing your own DNA is a grey area: it is not illegal because it belongs to you, but it may be illegal to distribute that DNA to somebody else, even by sexual contact. It’s important to understand that a gene edit done by CRISPR is inheritable.

There is a long list of diseases, and debilitating neurological conditions, clearly associated with certain genes and more genetic linkages to diseases are being discovered all the time. Diabetes, thalassemia, Parkinson’s disease, Huntington’s disease, ALS (a progressive neurodegenerative disease), certain heart diseases, epilepsy, obesity, cancer, all have associated genes. 

CRISPR could also be used to excise HIV and similar viruses. It has enormous applications in medical research.

It would be very tempting for wannabe parents to take DNA tests to identify dangerous genes they may possess and edit them out of the mix when making babies. 

Then again, genes are also associated with desirable traits, such as malaria-resistance, faster muscle building, greater lung capacity, slower resting pulse rates, better hearing, sight, and so on. 

Again, it is tempting for a wannabe parent to insert these genes and thus, create super-babies.

Of course, there are huge risks involved in such experiments. Experiments with non-viable and viable human embryos have had a hit-and-miss record so far. (A non-viable embryo cannot grow into a baby. It usually occurs naturally as a result of two sperms having fertilised the same ovum.)

Experiments in China, UK, USA and Sweden have high failure rates. This doesn’t mean it can’t be done, and as such experiments continue, failure rates will reduce. Charpentier is working on thalassemia at the moment.

And, an experiment in a US laboratory has demonstrated that removing a gene that causes an inheritable heart condition is possible.

Quite apart from the risks in terms of creating damaged babies, there is a really dark side to the equation. 

Genetic editing could also be done to create “socially acceptable” babies. In racist societies that could mean editing for cosmetic standards, such as certain shades of skin or hair colours that are considered beautiful and racially acceptable. It could also mean attempts at editing out genes that are associated with LGBT orientation.

Reaching beyond this, there are trans-human possibilities. Some sharks and whales live for over a century. Pigeons can detect magnetic fields. 

Cats can see in the dark and hear well beyond human range. Many animals have very sharp olfactory senses. Salamanders can regenerate organs. 

Inserting such genes into humans still sounds like science fiction but it could become mainstream science.

Scientists are still groping for consensus on the ethical boundaries of gene editing. It’s likely that different nations will set different limits, as has occurred with GM foods.

But as the technology of genome engineering is being commoditised, somebody, somewhere will, sooner or later, push the boundaries of what is considered acceptable.