In the latest episode of Genetics Unzipped, presenter Kat Arney takes a look at the history of gene editing, from the early days of restriction enzymes in the 1960s through to the CRISPR revolution and the very latest base editing techniques.
But while these tools are undeniably powerful and hold great promise for treating disease, with great power comes great responsibility. Kat asks what are the acceptable limits of genome engineering in humans, and will we see more CRISPR babies in the future?
The early days of genetic engineering
Almost as soon as the structure of DNA and the genetic code were discovered, scientists started looking for ways to change them. First they started by bombarding plants with radiation to cause mutations, before quickly moving on to more sophisticated editing tools – restriction enzymes.
The budding field of genetic engineering quickly adopted restriction enzymes to create hybrid DNA and modified organisms ranging from bacteria that produce synthetic insulin to longer-lasting tomatoes.
Next came more targeted editing tools, known as zinc finger nucleases and TALENS, which briefly enjoyed a couple of years in the genome editing limelight. But in 2011 came the discovery that would change everything: CRISPR.
Hello, CRISPR
The origins of CRISPR start back in 1987, when Japanese scientist Yoshizumi Ishino discovered repeating sections of DNA in bacteria. His paper ends with the immortal words “So far, no sequence homologous to these has been found elsewhere in prokaryotes, and the biological significance of these sequences is not known.”
Spanish researcher Francisco Mojica investigated what he called “Clustered regularly interspaced short palindromic repeats” (CRISPR) further, realising they formed some kind of bacterial immune system.
Then in 2011, Jennifer Doudna and Emmanuelle Charpentier showed that CRISPR, together with an enzyme called CAS9, could be used as a highly targeted, programmable genome engineering tool.
Other researchers made similar discoveries around the same time, including Lithuanian molecular biologist called Virginijus Siksnys and Feng Zhang at the Broad Institute at MIT, and there has been a fierce patent battle over the past decade since the technology was first invented.
The future of genome engineering
CRISPR-based therapies are rapidly making their way to the clinic for conditions such as sickle cell anaemia and genetic sight loss.
In 2018, Chinese researcher He Jiankui made headline news around the world when he announced the birth of twin girls, named Lulu and Nana, whose genomes had apparently been genetically altered to make them immune to HIV infection.
Alongside the ethical outrage, there are still scientific questions about how well the technique worked, and there is currently a global moratorium on human germline editing.
The field of gene editing is moving at break-neck speed, with ideas that would be considered science fiction less than a decade ago, like correcting single DNA letters to cure disease or making GM babies, fast becoming a reality.
But while these powerful tools offer genuine hope for people suffering from incurable genetic conditions, we should also make sure that they are used responsibly, so the consequences of their use remain positive for everyone.
Listen to the Genetics Unzipped podcast
Listen to the whole episode and find show notes and a full transcript at GeneticsUnzipped.com.
Genetics Unzipped is the podcast from the UK Genetics Society, presented by award-winning science communicator Dr Kat Arney and produced by First Create the Media. Follow Genetics Unzipped on Twitter @geneticsunzip, and the Genetics Society at @GenSocUK
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