News - June 28, 2018

Carefully cutting into genes - Spinoza winner John van der Oost: 'CRISPR-Cas is genuinely revolutionairy'


Last week, John van der Oost received the ‘Dutch Nobel Prize’. There are rumours that the Wageningen professor of Microbiology could be about to get a real Nobel Prize for his groundbreaking work on CRISPR-Cas. ‘But I try not to think about that so much. The Spinoza Prize is actually much better.’

text Nienke Beintema  photo Rafaël Philippen

Professor holding a personal chair in Microbiology John van der Oost: 'What we're doing is nothing new. We're just doing it much faster than in nature.'
Professor holding a personal chair in Microbiology John van der Oost: 'What we're doing is nothing new. We're just doing it much faster than in nature.'

CRISPR-Cas is the new buzzword in the life sciences these days. What does it actually mean?
‘CRISPR-Cas is a molecular system that enables you to cut DNA in specific places. That means you can essentially alter any gene in any organism. This “genome editing” is much easier, more precise and more efficient that other kinds of genetic modification. It’s truly revolutionary.’

What role did you play in its discovery?
‘CRISPR was discovered about ten years ago as a system in the DNA of bacteria. This is DNA in which small sequences of genetic code are continuously repeated. In 2005, foreign researchers discovered that there are fragments in that DNA that are identical to pieces of virus DNA. That’s why they thought it was probably an unknown kind of immune system that bacteria use to protect themselves against viruses. In other words, it’s a system that recognizes an incoming virus and then renders it harmless. I found this so exciting that I decided to use part of the money from my Vici grant to discover how the CRISPR system works. We were one of the first groups worldwide to start working on this, so the timing was fantastic. We were able to show that this was indeed an immune system. And we showed for the first time that CRISPR-Cas is suitable for general genome editing.’

If there was no exchange of DNA, we would be still be bacteria crawling through the mud

So how does that work?
‘CRISPR DNA, which contains pieces of virus DNA, is like a database of intruders, a kind of archive of fingerprints. In order to use this information, that DNA has to be transcribed into RNA, a process that we know from the regular protein synthesis in every living cell. In this case, CRISPR RNA is made that guides DNA-cutting enzymes such as Cas to the right place in the virus DNA. Cas will only bind to that DNA and cut it if there is a match. As soon as an enzyme cuts the DNA of a certain cell, repair proteins try to mend the break. In many cases there are small errors that lead to the inactivation of that gene. But you can also insert a completely new piece of DNA where the cut took place.’

Is this already being done in practice?
‘This is already being used a lot in biotechnology to give microorganisms and plants certain desired properties. Companies are using the CRISPR technique on bacteria and fungi to improve the production of biofuels, for example. It works extremely well in plants too. In the US, for example, there are apples on the market than no longer turn brown after you’ve cut them. There are also many examples of successful genome editing of human cells. For example, you can silence genes in a targeted way to study what their precise function is. A next step would be to make people better, but that’s still a long way off for most genetic diseases.’

Are there also ethical issues?
‘Yes, anything to do with genetic modification is still treated with suspicion. But CRISPR-Cas is not actually any different to what happens in nature. If there was no exchange of DNA, we would still be bacteria crawling through the mud. What we’re doing is nothing new. We’re just doing it much faster than how it happens in nature.’

What are the most promising applications?
‘You can make crops resistant to drought, disease or salinization, or you can significantly increase yields. With the world population constantly on the rise, that could become extremely important. You can have microorganisms make certain medicines, or biofuels or bioplastics. Of course we have to make quite sure that the end products are safe and healthy. But in my opinion this debate has started to spiral out of control. CRISPR allows us to make extremely precise changes to DNA. It’s a wonderful technique that lets us do many great things.’

Are people insufficiently aware of this?
‘Yes, I think we made mistakes in that respect, especially in the past. As scientists, we should have explained the story of genetic modification better decades ago. I think the most important thing is to emphasize the huge challenges we’re facing, from global food security to climate change and the depletion of fossil fuels. We have to give better explanations of what’s possible now, but also what the dilemmas are.’

What's the regulatory situation?
‘Within the EU, any changes at the DNA level that aren’t spontaneous are covered by the strict rules for genetically modified organisms. So they look at the process rather than the end product. These rules still stem from a time when there was much less knowledge and far fewer technical possibilities. Legislation in the US has already been relaxed: genetic modification is allowed there as long as the end product can’t be distinguished from what could happen in nature itself. We have to talk about that more at the European level.’

The CRISPR-Cas work is rumoured o be about to get a Nobel Prize, but there's a lot of haggling about who should get it.
‘Yes, that’s right. In a column in a Dutch newspaper, Piet Borst predicted that that Nobel Prize would go to the people who are working on the most spectacular human applications rather than the microbiologists who laid the foundation for that. He thought that was a pity. I thanked him for his column at the time. But I try not to think about it so much. The Spinoza Prize is actually much better. It’s fine this way.’

What are you going to do with the 2.5 million euros?
‘As far as bacterial immune systems are concerned, we only have the tip of the iceberg in our sights at the moment. At Wageningen we have identified a few systems that are comparable to CRISPR-Cas but can do slightly different things. I would like to investigate these systems further, and make improvements by creating synthetic variations. Perhaps there yet are more natural variations. And so we dream on, that’s the beauty of our profession.’