Page URL:

A Nobel for CRISPR genome editing – and for women scientists

2 November 2020
By Professor Matthew Cobb
University of Manchester
Appeared in BioNews 1070

The 2020 Nobel Prize in Chemistry has been awarded to Professor Emmanuelle Charpentier and Professor Jennifer Doudna 'for the development of a method of genome editing' known as CRISPR (see BioNews 1067). This award was long awaited, because their discovery, even though it was announced only in August 2012, has transformed the life sciences, and has the potential to transform medicine and agriculture.

Other, cumbersome and complex genome editing methods were available before, but the power, relative simplicity and low cost of CRISPR has changed everything. In 2011, fewer than 90 papers were published on CRISPR. In 2019, there were nearly 5500. Professors Charpentier and Doudna's August 2012 article in Science has been cited over 5500 times. These figures give a powerful impression of the impact of their discovery.

CRISPR allows researchers to use the cell's basic DNA repair mechanisms to alter a gene at will. The 'editing' metaphor is quite appropriate – just as you copy and paste letters in a word processor, CRISPR enables researchers to remove, insert or alter bases, or sections of DNA. CRISPR works in virtually every organism it has been used on, allowing researchers to genetically manipulate previously intractable systems. The creation of mutations and the exploration of their function, which was previously limited to a handful of 'model' organisms, is now possible in virtually any system. This has already changed how biology is performed, leading to new insights in a wide range of organisms, from ants to pigs and from potatoes to cabbages.

Above all, CRISPR contains the potential for new practical applications. It has been tested with apparent success on one of the most widespread genetic diseases – sickle cell disease – potentially transforming the lives of tens of millions of people. And there is also the prospect of rapidly developing new plants that will be able to respond to the changing climate and will be more acceptable to the public than current genetically modified crops because of the precision of the CRISPR editing system which simply alters the target DNA.

CRISPR has also raised darker, more profound questions, by enabling us to change human genomes, too. Notoriously, in 2018 Chinese researcher Dr He used CRISPR to manipulate human embryos in what he thought would be a major breakthrough (see BioNews 977)). However, the system he used was less precise than he believed and new mutations were introduced – these babies are now being closely observed, while Dr He is in prison. For both technical and above all ethical reasons, most researchers are opposed to using CRISPR to introduce changes in human DNA, which can be passed down the generations.

As always, behind the prize headline focusing on two brilliant researchers, there is a long and complex history. Odd repetitive sequences in the DNA of E. coli were first noticed by Japanese researcher Dr Yoshizumi Ishino and his colleagues in 1987, but were essentially an object of curiosity. In the 1990s a handful of researchers around the world showed that these sequences were found in many other microbes, and gave them their acronymic name CRISPR – clustered, regularly interspersed palindromic repeats (the 'palindromic' part is pretty approximate – most of them are not really palindromes). CRISPR has a nice sound to it, but the researchers toyed with the idea of calling the sequences SPIDR.

In 2005, Professor Francisco Mojica of the University of Alicante, Spain, showed that the 'interspersed' sequences – the bits between the palindromes – were of viral origin. This implied that the microbe had resisted viral infection and trapped these sequences – Professor Mojica suggested that it might act as a kind of immune system. Strikingly, his article was rejected by all the leading journals as being of insufficient interest, and it spent over two years trying to find a home.

In 2008, researchers from Holland, the UK and the US showed that small RNAs produced from the CRISPR sequences guided antiviral defence in microbes. By reading off the viral DNA trapped in their genomes, the microbes were able to produce guided enzymes that would snip up invading viral RNA.

This demonstration was the starting gun for a global race to understand both how exactly this 'immune system' worked, and above all to harness it for gene manipulation in other organisms. Both Professors Charpentier and Doudna have told me that as soon as they saw how the CRISPR system worked they realised it could be reprogrammed if a way could be found to use RNA provided by the researcher, rather than viral RNA.

Professor Charpentier at Umeå University, Sweden, and Professor Doudna at the University of California, Berkeley were both working on how CRISPR and its linked sequences (these are imaginatively called Crispr Associated Sequences), which code for various enzymes, are able to carry out their immune function, targeting invading nucleic acids. Their collaboration – and that of their junior colleagues, Dr Martin Jinek and Dr Krzysztof Chylinski – who were joint first authors on the key 2012 paper – led to the breakthrough where they were able to reprogramme the system and get it to alter a sequence in a precise manner that they had chosen.

But they were not the only researchers who had realised the possibilities. Professor Virginijus Siksnys and his colleagues at Vilnius University, Lithuania, narrowly missed out on being the first to turn CRISPR into a genome editing system – their 2012 paper describing their findings was rejected without review in April. It was stuck in review in another journal when Professors Doudna and Charpentier's paper appeared in Science in August. In the field, Professor Siksnys' contribution is widely recognised, and in 2018 he shared the prestigious Kavli prize with Professors Doudna and Charpentier.

The widespread approval of the 2020 Nobel Prize in Chemistry is not just based on the enormous significance of the discovery, it is also because the award has been given to two women – the first time that this has happened for any Nobel prize. Whatever we might think of the prize system – and there are plenty of reasons to criticize it for focusing on the contributions of only a handful of individuals – this particular prize may have a transformative power beyond the discovery it was awarded for.

As Professor Charpentier said on hearing the news: 'My wish is that this will provide a positive message to the young girls who would like to follow the path of science, and to show them that women in science can also have an impact through the research that they are performing.'

14 June 2021 - by Eleanor Taylor 
The genome editing capabilities of the CRISPR/Cas9 approach have created an enormous amount of excitement and an equal amount of concern within the scientific community. It is therefore unsurprising that this contentious form of biotechnology has entered the cultural zeitgeist and become a key topic of public interest...
4 May 2021 - by Devika Sooklall 
This genetic society podcast gives us a brief look into the history of genome editing and the various techniques that have been developed that have led us to where we are today...
25 January 2021 - by Tsvetana Stoilova 
A new natural feature of CRISPR/Cas9 which decreases gene activity rather than cutting DNA has been identified in bacteria...
12 October 2020 - by Dr Eleanor Lynam 
Professors Emmanuelle Charpentier and Jennifer Doudna have been awarded the Nobel Prize in Chemistry for their development of CRISPR genome editing...
6 April 2020 - by Julianna Photopoulos 
Academic and industry researchers led by Professor Jennifer Doudna, a pioneer of CRISPR genome editing, have opened a new COVID-19 testing centre at University of California (UC) Berkeley...
17 June 2019 - by Shaoni Bhattacharya 
GlaxoSmithKline is to partner with leading researchers at the University of California to harness CRISPR/Cas9 genome-editing to find new medicines...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.