Genetic Engineering: The Genie is out of the Bottle

Genetic engineering-CRISPR

It is one thing to predict that a breakthrough is imminent but it quite another to actual effect that leap forward. After researchers with cheery optimism had cried wolf on numerous occasions, the scientists & technologists have finally found an inexpensive and undemanding method of editing DNA. 

How is this feat performed and will it be the panacea as predicted?

Main picture: CRISPR will be the game changer. The die is now cast and genetic engineering will now be a reality

CRISPR is not the latest chip craze nor is it the latest type of cell phone. It’s name was certainly not decided on a cavalier whim but CRISPR – pronounced CRISPER – is the acronym for Clustered Regularly Interspaced Short Palindromic Repeats.

It is fitting that this truly remarkable breakthrough will be used in its inaugural test at London’s Francis Crick Institute. Francis Crick passed away in 2004 but James Watson, the co-discoverer of the structure of DNA, now 88 years old and truly in the evening of his life, must be elated.

Designing one's own baby

Designing one’s own baby

Contrary to some narratives, even the Human Genome Project did not advance genetic engineering per se. What Kathy Niakan will do is to inject a specially prepared liquid into an embryo, an egg that has been fertilised with a sperm. If all goes as expected, the liquid will alter the DNA at the core of the cell. In effect Niakan would have succeeded in editing the DNA of the embryo.

Despite CRISPR – or to give it is full name CRISPR-Cas9 – being only four years old, it is a truly a transformative discovery. The implications of its potential uses extend far beyond the treatment of diseases to the development of hardier fruits and even the production of ethanol. The possibilities are endless. Perhaps even Steven Spielberg’s envisioned recreation of extinct species is no longer a fantasy but an imminent reality.

Kathy Niakan - the gene sleuth

Kathy Niakan – the gene sleuth

In genetics, it is not just the DNA which is the key to genetic engineering but also RNA. Relating these to the alphabet and spelling, the DNA is the genetic alphabet whereas the RNA spells the actual words. What has transpired recently is that a scientist at MIT has developed a method to edit the RNA making CRISPR even more potent.

The Roadmap to today

The discovery of the double helix by Francis Crick and James Watson in 1953 was not without controversy. The story of the unveiling of the double helix is messy and complex, just like all biology. It has been pored over and studied and embellished and mythologised. Simply put, the race was won by Crick and Watson, and in April 1953 they revealed to the world the iconic double helix. The key evidence, however, Photo 51, was produced by Rosalind Franklin and Ray Gosling, at King’s College London. Franklin’s skill at the technique known as X-ray crystallography was profound, and was indubitably essential to the discovery. Crick and Watson acquired the photo without her knowledge.

Francis Crick and James Watson, the co-discoverers of the double helix structure of DNA

Francis Crick and James Watson, the co-discoverers of the double helix structure of DNA

Contrary to some narratives, Franklin was not overlooked by the ultimate accolade – the Nobel Prize. The rules are quite clear: Nobel Prizes are not awarded posthumously. Franklin had died from cancer aged just 37, in 1958, four years before the Nobel committee recognised what is undoubtedly one of the most significant scientific advances of the 20th or indeed in any century.

With their unique insight and vision, Crick and Watson indubitably deserve their Nobel gongs.

Rosalind Franklin - highly adept at X-ray crystallography

Rosalind Franklin – highly adept at X-ray crystallography

More recently in 2007, James Watson has become embroiled in a racist foray regarding his belief that black co-workers were slow learners. Perhaps this is harking back to the views of the controversial eugenist, Francis Galton. If so, the mores the pity that such an eminent person should stain his reputation by supporting such a debunked theory.

The next leap was to dismantle the DNA in order to understand which genetic aberrations contribute to disease.

Mapping the genome came next between 2001 and 2003. This process was to determine the master plan of DNA.

Craig Venter - Mapping the genome

Craig Venter – Mapping the genome

Finally came the excising of aberrant DNA using enzymes. With the inexactitude of the methods employed, genetics entered the proverbial doldrums. Aside from the risks associated with an inexact & unpredictable process, these methods all had a common nemesis, the time taken to perform.

The eureka moment

There is something compelling in the serendipity of how most discoveries are made.  So it was with CRISPR. Luck has everything to do with it. Harked back to Alexander Fleming’s discovery of penicillin, the method to edit DNA was unlocked by a humble cup of yoghurt. A bacterium that provides the yoghurt with its particular tang was continually being infected by a virus thereby altering the taste of the end product.

Alexander Fleming

Alexander Fleming

On sequencing the genome of the bacteria, the researchers found odd repeated fragments of DNA. In a light bulb moment, one of the scientists realised that these repeated fragments were not random and should not be ignored. He speculated that these fragments were the bacteria’s method of record keeping. It was a genetic record of viruses that had infected them. In effect it was a crude but effective immune system.

Furthermore according to the Time Magazine in an article entitled Life, The Remix, “Rodolphe Barrangou’s critical insight was that between the repeated sections of DNA were snippets of the virus’ DNA. When the same virus attempted to re-infect the bacteria, it would gravitate towards the matching section on the bacterial genome and bind to it. That summoned a powerful enzyme that effectively snipped the virus out, leaving the bacterium free from infection.

Rodolphe Barrangou

Rodolphe Barrangou

This discovery while revolutionary in itself, it still required another breakthrough in determining how to employ this procedure in the real world. A world-wide team was formed to determine the mechanism. The ultimate breakthrough was discovering that an enzyme named Cas9 could function as a powerful pair of genetic scissors. By loading a matching RNA sequence into CRISPR, the researchers were able to target a specific section of DNA. Once paired, the Cas9 enzyme would cut out the matched section”

 Immediately this technique was hailed as monumental.

Six months after this discovery Feng Zhang at MIT used the technique on a human cell for the very first time. It was a success. CRISPR could edit the DNA of human cells precisely and efficiently. Not only that, but a CRSPR kit is extremely cheap at $130

Editing a gene using the CRISPR technique

Editing a gene using the CRISPR technique 

The welter of projects already underway using this technology is limited to the researchers’ imagination such as turning genes off in a tumour to make them more susceptible to the immune system or to the deactivating 62 genes in pigs so that they can grow spare parts for humans. They are currently even designing bacteria that will speedily consume waste plastic.

Apart from the inherent dangers in playing God with the human genome, there are concerns that this technology could be employed for biological warfare purposes. Here the concerns relate to the creation of superstrains of diseases that could literally wipe out whole populations.

GM creature

GM creature

Inherent in any new technology there are similar concerns except that in this case the stakes are higher.

Much higher.

But the genie is now truly out of the bottle. Once it is out, it is extremely difficult, if not impossible, to reinsert.

Hold on tightly and enjoy the ride.

 


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