What if tomatoes grew deeper roots, so that they could thrive in dry regions? Would we be able to better feed the increasing global population? The CRISPR-Cas technology that enables such adjustments is much more precise than the typical selective breeding method, and the adjustments are comparable to spontaneous natural changes. But is this technology, for which many significant principles were discovered by Wageningen scientists, actually safe? Who will benefit from it? Where do you see opportunities for its use?
“The CRISPR system holds great promise for helping to feed the world. Specifically, we can use it to improve plants. And that can be done much more precisely than with typical selective breeding, so that only minimal changes are necessary”, says John van der Oost. The Wageningen Professor of Microbiology has made a significant contribution to unravelling the mechanism behind the CRISPR-Cas system, which enables bacteria to render viruses harmless (see box). CRISPR-Cas is used in biotechnology to improve the traits of food crops and in the production of biofuels and medications via micro-organisms. Furthermore, it has a practical use in medicine: improving the health of patients with certain genetic illnesses.
What is CRISPR-Cas?
CRISPR-Cas is an anti-virus system found in bacteria. Many species of bacteria have small strands of repeating DNA in their chromosome, separated by variable strands. Together, these form the “CRISPRs”. In addition to the CRISPRs, there are also Cas proteins, which seek out and cut specific locations in the DNA.
About ten years ago, John van der Oost and his colleagues discovered that this was a unique defence system that bacteria used against invading viruses. The bacteria takes some genetic material from the virus and incorporates it into its own DNA. Copies of this CRISPR-DNA (called CRISPR-RNA) form complexes with Cas proteins, which are “on patrol” throughout the cell. As soon as the virus makes its way inside again, the CRISPR-RNA recognises the enemy. The Cas enzyme cuts the virus’ DNA into pieces and eliminates the threat.
The research in Wageningen also showed that you can use CRISPR-Cas to cut a specific location in the virus DNA. Later on, it became evident that this system could also be inserted into bacteria, plants, and animals — including humans — in order to cut DNA at specific locations. A strand of CRISPR-RNA that is inserted along with the Cas enzyme serves as a guide to the desired location.
Half of all bacteria species use a CRISPR-Cas system. In recent years, it became clear that there were many CRISPR-Cas variants. These systems can vary significantly in their actor mechanisms, precisions, etc.
Watery tomatoes
Van der Oost illustrates what CRISPR-Cas can do for crops using tomatoes. Tomatoes were once unremarkable, small fruit from the South American jungle. People have been cross-breeding different variants for hundreds of years and, over the past 60 years, they have even exposed tomato seeds to chemicals and radiation, called “classical mutagenesis”. The preference was for large, fast-growing tomatoes. Therefore, the tomatoes that you currently find at the greengrocer and supermarket are very different from the natural variety.
“In tomatoes, a lot has been changed at the DNA level, to the extent that even positive traits have been lost”, says Van der Oost. For example, in older forms of selective breeding, taste was not a priority. Many people may still remember the tasteless, watery tomatoes from 20 years ago in the Netherlands. “The old forms of selective breeding were like taking shots in the dark: you accidentally activated and deactivated genes. In addition to suffering from a loss of flavour, tomatoes have also lost nutritional value and resistance to bacteria and fungi.”
Photo of a breakthrough experiment in 2008
Minimal mutations
Last year in Wageningen, the DNA of several selectively bred tomatoes and wild jungle tomatoes were compared. Van der Oost: “You can see that 1-2% of the DNA is completely different. The total genome consists of 1 billion base pairs, which are the building blocks of DNA. Due to years of selective breeding and mutagenesis, the tomatoes we grow today have 10-20 million different base pairs.” “Using CRISPR-Cas, scientists recently deactivated six genes in the wild tomato with great precision in order to ensure that it grew larger and faster, but also retained its flavours, nutritional value, and resistance”, explains Van der Oost. “Only 30 base pairs were changed. Minimal changes such as these are similar to the genetic mutations that spontaneously occur in nature.”
“ The minimal changes that we cause with CRISPR-Cas are similar to the genetic mutations that spontaneously occur in nature. Using this technology, we can substantially improve the production of food crops. The exceptional precision of the CRISPR-Cas method means that the flavour, nutritional value, and resistance to disease will not be affected.”
John van der Oost, Professor of Microbiology
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Improvements
So much has been learned about CRISPR-Cas that the technique can now be applied very quickly and accurately. “The first CRISPR systems that we used to conduct research, sometimes made changes to locations just in front of those that we were targeting. We have since discovered CRISPR enzymes in other naturally occurring bacteria that are even more precise.” The microbiologist worked with a small company to seek out bacteria that could break down stems from agricultural waste. It turned out that they were right around the corner, in a compost heap in Ede. These bacteria also had a stable CRISPR system. “There are tens of thousands of variants with their own interesting traits and the search for them is fully under way. Our research contributes to improving precision and, in turn, safety”, says Van der Oost.
European concerns
In Europe, there is a great deal of scepticism and concern surrounding CRISPR-Cas. In 2018, the European Court of Justice decided to include CRISPR-Cas technology as a method of genetic modification. This means that a long process of safety tests must be conducted prior to use. The situation is different in countries such as the US, Canada, China, Japan, and, recently, Russia. “In these countries, making small changes with CRISPR is not considered modification, because small changes like these occur very frequently in nature as well”, explains Van der Oost. “The EU is taking the moral high-ground here, but, in my opinion, it isn’t the brightest decision. For smaller selective breeders and biotech companies in European countries, this is practically a death sentence, because they are losing their global position among the competition.”
Considerations
Van der Oost understands the scepticism, but stresses the differences when compared to traditional selective breeding. “All our vegetables and fruit, even from organic farmers, have been changed so much that they can no longer be found in nature. On the other hand, the small changes using CRISPR-Cas are so similar to the natural process that they no longer differ from what naturally happens in plants.”
Conference on CRISPR-Cas
Do you want to join the discussion? Come to “CRISPRcon. Conversations on science, society and the future of gene editing”. At this conference on CRISPR-Cas, we will hold an open dialogue, exchanging perspectives, visions, and concerns. CRISPRcon will take place on 20-21 June 2019 in Wageningen. Information and registration.
In order to help further the debate between opponents and proponents, the Rathenau Institute argues for a holistic consideration of the social use, sustainability, and ethical aspects of CRISPR-Cas. “It is a shame when proponents and opponents dig their heels in the sand and end up standing in the way of innovative developments. It would be a good idea to look into whether the technique is safe and has an identifiable use for society and, in doing so, attempt to get this stalled debate in motion again”, says Van der Oost.
Climate change
In Van der Oost’s opinion, using CRISPR-Cas to improve food crops can deliver a lot of other benefits. The crops can begin to closely resemble their wild counterparts once again, becoming more delicious, nutritious, and resistant to disease and pests. However, even more than that is possible. “Imagine that climate change causes a drought in a region. If we make targeted, minimal changes to a tomato, allowing it to grow deeper roots, the tomatoes will still be able to thrive. There are a lot of great things that we can do with CRISPR-Cas, from which farmers and consumers in Africa and Asia could also benefit.”
In 2018, John van der Oost received the Spinoza Prize, the highest scientific distinction in the Netherlands, for his ground-breaking work on the CRISPR-Cas technology. “I am convinced that we can do many great things with CRISPR-Cas. This technology would benefit everyone: selective breeders, farmers, shop owners, consumers, etc. Not to mention that it could be used across the world: from the Netherlands to areas of Asia and Africa, where the situations pose greater challenges. I am aware that we should not make too many promises, but if we want to help feed a growing global population on a planet with a rapidly changing climate, then we have to continue improving crops in a fast, accurate, and safe manner with all the tools at our disposal.”
Greetings,
I reside in the West Indies, island of Trinidad and Tobago. I have been reading of the great inventions performed by Pro. John van der Oost, and his team. I would appreciate a contact with the Prof. to discuss issues related to the production of vegetables in tropical climate conditions threatened by the effects of insects and dry/wet soil characteristics.
Greetings,
I reside in the West Indies, island of Trinidad and Tobago. I have been reading of the great inventions performed by Pro. John van der Oost, and his team. I would appreciate a contact with the Prof. to discuss issues related to the production of vegetables in tropical climate conditions threatened by the effects of insects and dry/wet soil characteristics.