In February 2019, chefs in the U.S. state of Minneapolis became the first people able to work with Calyno, a soybean oil with a healthier fatty acid profile developed using the gene editing procedure TALEN. The genetic mutation created in the laboratory soybean cannot be distinguished from natural mutations, which is why the plants can be cultivated without any special requirements and the oil marketed in the U.S. as “GM-free”. In Europe, soybeans such as these are considered genetically modified and are banned for the time being. The EU intends to decide how to proceed with gene editing procedures, such as TALEN and the more widely known molecular scissors CRISPR / Cas9, in 2021.

Jörg Huthmann

Its proponents argue that the only way to safeguard the global food supply against population growth and climate change is through new cultivation methods, including genetic engineering, whereas its detractors cite the lack of research into the on-target and off-target effects of gene editing.

What’s certain is that genetic mutation is a process that takes place naturally and is vital to maintaining biodiversity. Plant growers attempt to use mutations to permanently retain beneficial qualities in certain plants in subsequent generations. Here, mutations are provoked through chemical processes or ionized radiation, with the latter also known by the less-flattering term “atomic gardening.” These conventional methods initially produce random mutations. Selecting new plant properties was and remains a process that takes years, as it is based on this random process. But now, new gene editing procedures have changed all that. The CRISPR / Cas9 molecular scissors remove the element of chance and enable precise mutations to be defined in a genome.

Anything is possible

This may lead to new sources of food being identified, or cures for hereditary diseases found. Any living organism, including human beings, can be genetically edited using the process, which is why it is vital that a responsible approach is taken and clear political frameworks put in place. This is the area that is attracting the most criticism from many NGOs. The work of scientists and researchers is not viewed with skepticism, nor are the current and future possibilities of using the new tools. Criticism mainly centers on the promises of organic-led farming that were not kept when existing methods of genetic engineering were discovered. There is concern that CRISPR and co. will be used to maximize the profits of the industry’s major players when it comes to seed and crop protection, and not serve to advance sustainable farming.

State-of-the-art IT plays an essential role in the success of the process, as gene sequencing produces enormous amounts of data. Every single person carries around 25,000 different genes. The first DNA sequencing of a full human genome was completed in 2000 after work lasting years and costing millions. Since then, the costs and the workload have fallen significantly. Wheat – a staple in the global food supply alongside rice, corn, and soy – has a much larger and more complex genome than human beings. Decoding and documenting the genetic information of an agricultural crop in combination with the CRISPR / Cas9 molecular scissors opens up brand new dimensions in the world of plant cultivation.

What is CRISPR / Cas9?

CRISPR / Cas9 is a molecular biological method of adding, removing, or deactivating genes. The acronym CRISPR stands for clustered regularly interspaced short palindromic repeats. The Cas9 suffix refers to a protein that allows the CRISPR method to function. U.S. scientist Jennifer Doudna and Emmanuelle Charpentier, from France, were the first to decode the molecular scissors in 2012, and their efforts were rewarded with the Nobel Prize in Chemistry in 2020. Doudna lectures at the University of California in Berkeley, whereas Charpentier has been the Head of the Max Planck Unit for the Science of Pathogens in Berlin since 2018. Their discovery showed that bacteria have a rudimentary immune system that prevents external (viral) DNA from entering. This defense mechanism proved to be a universal tool.

Prof. Dr. Karl-Heinz Kogel,

Professor of Phytothology at the Justus-Liebig University Giessen, holds some specimens of his research subject in his hand: wheat plants. Kogel’s working group developed the CRISPR / Cas9 technique for barley to edit the genome of grain plants with high levels of efficiency.

Karl-Heinz Kogel, Professor of Phytopathology at the Justus-Liebig University Giessen, is one of the world’s leading experts in this area. Kogel and his team conduct research on plant protection, plant disease, and crop biotechnology.

Professor Kogel, GMO is an extremely divisive subject. In which direction are you heading with your current research projects?

We are mainly looking into to biological plant protection and making use of helpful microorganisms; gene editing is just one of many tools in this area. Blight-resistant wheat is achievable using conventional cultivation methods in ten years, but with CRISPR it only takes one.

Do you only see positives from the use of CRISPR / Cas9 compared to older plant cultivation methods?

RISPR is more precise, or in other words more selective. And, as I mentioned, it’s also significantly quicker than previous methods. It is an extremely useful tool in plant cultivation, but it still lacks political acceptance, or is a controversial subject at least, in Germany and in the EU. This attitude does not reflect the current scientific understanding, so I think the topic should be re-assessed. At least that’s happening now.

How do you view the off-target effects of CRISPR / Cas9, which critics often cite as one of the main risks?

I would cite my colleague Detlef Wiegel1, who noted in a recent interview that billions of off-target mutations occur in one hectare of wheat simply as a result of the sun’s UV rays. Politically, a distinction is drawn between mutagenesis due to natural factors and mutagenesis as a result of genetic changes. There is no way of differentiating changes to a plant genome generated through CRISPR / Cas9 from mutations that occur naturally; CRISPR / Cas9 mutations also cannot be retrospectively traced as such. Really the only difference is that the CRISPR / Cas9 method is significantly safer and more environmentally friendly than conventional mutagenesis methods. I don’t consider there to be any scientific reasons standing in the way of approving modern cultivation methods.

Do you think it’s possible that gene editing will gain a foothold in European politics?

My scientific viewpoint here is clear; it would be a very welcome development if it did. At the moment it appears as if the ban on gene editing is having the biggest impact on the small and medium-sized cultivators who provide so much diversity in the industry. CRISPR is simple and quick and would be an ideal tool for these cultivators to quickly apply agronomic improvements to approved plants in a targeted manner. These are the people being hampered by the current policies.

Are we perhaps having the wrong discussion here, and is there a way out of this dilemma in your opinion?

Here in Germany we are a leading force in plant sciences, together with China and the U.S., and at the moment there is still sufficient funding for our research. The problem is that we frequently bring high-level developments to the table but do not find any partners in Europe to implement the findings in practice, because of the political restrictions. Patents are one way of protecting knowledge, as are partnerships with major companies. Both of these are taking place, but there is a bottleneck when it comes to making use of the latest scientific findings in the field. This is where we need forward-thinking national and EU-wide regulations. Without these, we will lose our world-leading status.

1 Prof. Dr. Detlef Weigel is a Director and Scientific Member at the Max Planck Institute for Developmental Biology, Tübingen, Germany, among other roles.

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