“Gene editing is not new,” Professor Emmanuelle Charpentier started off at #LINO70. It’s been done for decades in one form or another, but we’re still just at the start of the road. For instance, the CRISPR/Cas9 genetic scissors pioneered by Charpentier and her collaborator Jennifer Doudna opened a whole new avenue in gene editing. In a set of talks, Nobel Laureates and leading researchers discussed the advantages and opportunities gene editing offers, but also the ethical challenges it brings.
You could hardly imagine a better topic for a #LINO70 lecture than CRISPR/Cas9. It’s not just that Charpentier and Doudna were awarded the 2020 Nobel Prize in Chemistry, but the method has progressed immensely in a short period of time. In 2012, the landmark paper presenting the last steps of the procedure was published, and by 2014, there were already 1,000 published studies. Now, we’re nearing 20,000 published papers, and several clinical trials using the method are well underway.
CRISPR/Cas9 is already used as an experimental method to treat sickle cell disease (a group of inherited blood disorders), as well as some forms of blindness – and this is just the tip of the iceberg. Increasingly, researchers already eyeing ways to deploy CRISPR/Cas9 to sickle cell disease and help millions fight hunger, by tweaking crops and making them more resilient to things like pests and climate change. “Things moved very fast,” Charpentier recalls. But they only moved so fast because the time was right.
The Right Time
Understanding and applying CRISPR/Cas9 required technologies that simply weren’t available a few decades ago; it was only thanks to recent advancements in biotechnology that the work of CRISPR pioneers was possible – a remarkable case of science helping science.
Hearing Charpentier talk about the method, calm and collected but with passion coming through every sentence, you can almost get a feel of the countless days she spent thinking not just about the method itself, but also its implications and potential. “In a way we are rewriting the code of life. For me, it’s more than editing genes, it’s also editing the DNA that may not be considered “genes”, like the DNA strands encoding protein.”
In addition to offering highly-sought precision, CRISPR/Cas9 has also offered unprecedented ease of gene editing. Charpentier points out that this has made the field more democratic and open, enabling multiple labs to play a role and refine and improve the technique even further. Many brilliant minds are working on it, and it shows – but there’s still room for progress. “CRISPR/Cas9 is one of the newest tools. It has become popular thanks to its simplicity and its ability to be delivered in a large number of cells and edit genes and their expressions,” Charpentier notes.
“I would like to see other gene-editing technologies coming up in the future to be combined with CRISPR and increase our ability to edit genes in an even broader and precise manner.” Molecular biotechnologist Julia Jansing, who’s worked with CRISPR since 2014, fully agrees: “I’m always surprised with how many more methods teams are finding,” Jansing notes. But for all its advantages and ease of use, CRISPR/Cas9 is not without some share of controversy.
The Good, the Bad and the Genetic Scissors
A stellar panel brought together Charpentier, Jansing, developmental biologist and Nobel Laureate Christiane Nüsslein-Volhard, and ethicist Alena Buyx. Along with moderator Adam Smith, the four discussed the potential and implications of CRISPR/Cas9 and gene editing in general. After a brief moment of enthusiasm regarding the benefits gene editing could bring, things quickly heated up when it came to the ethics.
“I join all my colleagues in their excitement,” Buyx said. “I’m a doctor by training and this technology has such amazing potential, not just for plants and animals, but also for treatment. That being said, what we have seen and I regret very much, was an event in 2018, when the so-called CRISPR babies were reportedly born in China.”
“I wish we didn’t have that experiment.” In 2018, Chinese scientist He Jiankui edited the genomes of human embryos – and not to cure them of any threatening health condition, but rather to make them less susceptible to HIV. The announcement shocked the world and immediately drew widespread criticism from researchers in the field. Although the babies were reportedly born healthy, he was swiftly sentenced to three years in prison and fined a hefty amount, but this was just the tip of the controversy.
Not long after, the World Health Organization issued a call to halt all work on human genome editing, and pressure grew for tighter regulations. At the panel, the two laureates argued that fears regarding gene editing are at least somewhat overblown. Checkpoints are already in place, and with the exception of rogue events like the one in 2018, the method is being used in a safe way that can benefit humanity. “We eat foreign genes all the time – you eat beef, you eat a foreign gene. This worry is irrational,” Nüsslein-Volhard quipped.
Part of the problem comes not from gene editing itself, but rather from the stigma it has around it. “I think the words that are used are important,” Charpentier added. The public has a conception […] that is quite negative, and I think it’s important to redefine this.”
“I would have thought that with the pandemics, the public has understood that what scientists do really does work”
In a subsequent Agora Talk, Nobel Laureates Tomas Lindahl and Sir Martin Evans discussed some of the ways regenerative medicine has benefitted from a better understanding of genetic processes. For instance, DNA damage is connected to almost all processes related to the ageing process, Lindahl explains – so that’s probably a good place to start looking if we want to tackle ageing.
But there doesn’t need to be any practical benefit to this research – or at least not directly. Oftentimes, understanding the underlying biology is more valuable down the road than finding an immediate use, Evans points out. At the end of the talk, Evans also left an important takeaway message for the young researchers at LINO70: “You don’t have to spend every minute of your day tied to the bench… you need a life. You ought to be interested in a lot of things that are not what you’re studying.”