Cutting the Code with CRISPR

CRISPR-Cas9 is a gene-editing breakthrough that promises cures for genetic diseases but raises ethical concerns about creating “designer babies” and potential misuse. While some advocate for a moratorium on germ-line modifications, others argue for its therapeutic potential, especially in eradicating devastating genetic disorders like Tay-Sachs.

This article was first published in The Mint. You can read the original at this link.

On 28 June 2012, Jennifer Doudna and Emmanuelle Charpentier published a paper in Science magazine describing CRISPR-Cas9, a revolutionary new gene-editing technique that makes it cheap and easy for anyone with a basic knowledge of molecular biology to directly edit DNA. Given that there are close to 6,000 diseases we know are caused, at least in part, due to genetic errors—missing or garbled sequences of DNA that result in the inability to correctly synthesize a specific protein—a tool like this will allow us to find cures for these ills by directly altering the genetic code.

But, even as biologists rejoice at the benefits that this new precision tool will bring, there is grave consternation around the legal and ethical implications that it presents. After all, DNA is the source code of life and we have to question whether we are ready to take on the responsibility that comes with being able to freely edit this code.

CRISPR-Cas9 will make it be possible for parents to ensure that mutations such as Huntington’s disease—an incurable condition that results in the inevitable breakdown of the brain—are eliminated from their children’s DNA. By the same token, it will give parents (who can afford it) the option to requisition specific hair and eye colour in their progeny or even design them to be healthier, smarter and stronger than they would have otherwise been. It will allow the privileged the power to create “designer babies" and inevitably perpetuate the divide between the haves (who can afford gene treatments) and have-nots.

In the hands of a biohacker, CRISPR-Cas9 could transform even the most benign infections into deadly epidemics and engineer them to replicate rapidly, targeting specific sections of society based on their genetic make-up. In terms of their potential to cause harm, this could be a weapon far easier to deploy and many orders of magnitude more dangerous than a nuclear attack.

Even experiments with apparently noble objectives could have drastic unintended consequences. There are labs in Harvard today that are experimenting with using CRISPR-Cas9 to insert malaria-resistant gene drives directly into the genome of the anopheles mosquito so that future generations of mosquitoes are genetically incapable of carrying the malaria germ. No one can accurately predict the long-term implications of this sort of manipulation, but given that they are germ-line modifications, it is not inconceivable that a poorly thought-through edit could result in the eradication of mosquitoes as a species.

It is primarily for this reason that the genetic community has called for a complete moratorium on germ-line genetic manipulation to ensure that any edits to the genetic code do not pass into the hereditary pool. More than 40 countries explicitly discourage or ban these experiments. The Indian Council of Medical Research, in its Specific Principles for Human Genetics and Genomics Research, has issued a prohibition along similar lines.

But there is another school of thought that challenges this conservative approach. They argue that medical science has always been about improving our odds of survival. Vaccinations gave us superhuman immunity; prosthetics were designed to replace limbs and damaged organs—even the drugs we consume are intended to reverse the effects of naturally communicated diseases that would otherwise have curtailed our life span. The goal of medicine has always been to create improved humans and CRISPR-Cas9 is just the latest tool that will help us along in that direction. Any ban on germ-line research will prevent us from reaping the therapeutic benefits of this technology.

Even if we can agree that there are risks inherent in meddling with the gene pool, we have to recognize that certain genes are bad in every conceivable context. Tay-Sachs is a rare genetic disease currently believed to be incurable. Children afflicted by it grow normally for six months, and then, without warning, begin to develop muscle weakness, loss of vision and hearing and seizures. They usually die before the age of four. Tay-Sachs is caused by a mutation in the HEXA gene that prevents the body from producing Hexosaminidase-A, resulting in the build-up of a fatty substance in brain and nerve cells that eventually destroys these cells.

There is no conceivable benefit in allowing a gene that causes this sort of pain and suffering in children to survive in the gene pool. Now that CRISPR-Cas9 makes it easy to target and remove specific gene mutations, there is no reason why we shouldn’t make appropriate germ-line modifications to permanently eradicate Tay-Sachs.

While we may be understandably wary of vesting god-like powers in the hands of human geneticists, we cannot let our fear of designer babies come in the way of our goal of ensuring that our babies are born healthy.