Author: cibuswpadmin

A short guide to answering a complicated question.

While Covid-19 has commandeered the world’s attention, an important debate that will weigh on the future of agriculture is in process in Europe. European regulatory agencies are assessing what constitutes a genetically modified (GM) product. This debate started in the last century, and it has been characterized by confusion, inaccuracy and inconsistency. Here is my ‘cheat sheet’ for what does — and what does not — qualify an organism as GM based on scientific discourse.

Settling GM vs. Non-GM

Broadest Definition: ‘GM’ means any genetic change in an organism. This definition is useless. Every food we eat — organic or not — is the product of genetic change. Without genetic changes fostered 10–12 thousand years ago by indigenous peoples in Mexico, corn would still be a tall grass with tiny kernels encased in tooth-breaking hard shells. Traditional plant breeding attempts to alter genes, as do all other plant-breeding techniques.

U.S. Regulatory Definition of GM: From a U.S. regulatory perspective, ‘GM’ is defined as introducing foreign DNA and inserting it into the genome in a place where it would not naturally occur. Organisms that do have such foreign DNA are called transgenic, and this applies to many large acreage row crops grown in the United States, such as Roundup Ready or insect-tolerant corn and soybean.

Additional Definitions: Certain non-government organizations (NGOs) have their own standards to classify a crop as ‘GM’. For certain groups like The Non-GMO Project, if any specific gene is targeted and altered (regardless of whether the technology introduces foreign genetic material into the genome), it is ‘GM’.

The question then becomes not if genes change, but how they are changed.

So, what technically constitutes a non-genetically modified organism, outside of the obvious? Non-GM can include selective breeding: a practice that farmers have been honing for millennia.

Selective Breeding (non-GM): Traditional plant breeding involves cross-breeding plants that possess desired traits, ultimately producing a plant with the better combinations of these traits. The process of looking at as many combinations as possible involves trial and error.

The Grey Area

And still, the GMO-classification debate has a murky grey area. Certain techniques such as mutagenesis and gene editing can fall into either camp, depending on how they are used.

Mutagenesis: This technique involves exposing the genome to specific chemicals or radiation with the goal of inducing mutations and the hope that among the mutants produced will be a plant with the desired trait. For the past 40 years, more than 3,000 products of mutagenesis have been sold and globally consumed without any negative effects.

Chemical mutagenesis produces beneficial mutations, as well as a large number of undesirable mutants (collateral damage). Conventional breeding techniques are used to retain the beneficial mutations and eliminate the collateral damage. Interestingly Canada has a product-based regulatory system — designed to ensure the quality of the product — novel traits are regulated. However, in the European Union, products of mutagenesis are generally accepted as conventional plant breeding. In both cases, mutagenesis technology is accepted as non-GM, or non-LMO (living modified organism) in Canada.

Gene Editing: This refers to the direct or indirect alteration of a plant’s genes. This category covers several different approaches with a wide range of processes and outcomes, and because of that it has generated significant confusion in the public, among NGOs, and even with policymakers.

Gene editing can take three paths: 1) gene knock out (inactivating specific genes), 2) precise changes in the genome at the smallest possible level, or 3) insertion of a transgene into a specific location within the genome. The first two outcomes occur regularly in nature, as typographical errors can occur each time DNA replicates. Further, methods using these techniques can either be transgenic — involving insertion of the editing tools themselves into the genome — or non-transgenic — without inserting tools. In some cases, transgenic tools are inserted and then removed from the final product, and in those instances, some regulatory authorities consider these crops to be non-GM.

Non-GM Gene Editing: As of today, we believe the non-GM gene editing technology with the greatest precision and flexibility involves the use of molecular scissors (where the editing tools are not integrated into the genome) in combination with a chemical construct (in scientific terms, an oligonucleotide) that triggers the genome’s own repair system to make precise changes in a particular gene. In other words, this technique — called Precision Gene Editing — triggers the genome’s spell-checking machinery to edit itself. Like a typographical error that can occur when the DNA sequence is copied, or even when chemical mutagenesis is used, the chemical construct leaves no trace once its work is complete. In no way does it become incorporated into the genome. Since transgenes are not involved at any stage in such edits, and because the oligonucleotide disappears after performing its job, this form of gene editing classifies as non-GM in many jurisdictions.

Where the Regulatory Debate Stands

During the 1990s, policymakers around the world developed and introduced regulations designed to assess the risks associated with the emerging transgenic technology that enabled developers to introduce foreign genes into crop plants. This technology was described as genetic modification (GM) technology and it enabled developers to introduce changes to plants that could not occur naturally. As this kind of change had not been seen before, policymakers adopted a precautionary approach and introduced very stringent regulations.

The stringent regulations have remained largely unchanged for over twenty years and have proved prohibitively expensive. As a result, they have limited the use of GM technology to a small number of large crops developed by a small number of large companies. Nonetheless, since 1994, more than six billion acres of GM crops have been planted worldwide.

Shortly after the dawn of the new millennium a technology emerged that could directly edit a plant’s genome without introducing foreign genetic material. For the past 10 to 15 years, policymakers have been working to understand the risks associated with the new emerging technology called gene-editing.

Among the scientific advisors to policymakers, there was an early consensus that when the gene-editing technology did not result in the introduction of foreign DNA, the resulting variety posed no more risk than conventionally bred varieties.

In 2015, the Argentina Biosafety Commission (CONABIA) was the first regulatory authority to address gene-editing. They determined that gene-edited varieties that contained no foreign DNA posed no greater risk than conventionally bred varieties and so they should be regulated in the same way as conventional varieties.

In the following years, the governments of Chile and Brazil adopted similar policy and in March 2018 the US Secretary of State for Agriculture, Sonny Perdue, issued a statement confirming that, under its biotechnology regulations, ‘… the USDA does not regulate or have any plans to regulate plants that could otherwise have been developed through traditional breeding techniques…’

In October 2018, the governments of Argentina, Australia, Brazil, Canada, the Dominican Republic, Guatemala, Honduras, Paraguay, the United States of America, and Uruguay issued a statement through the World Trade Organization with the primary objective to ensure that the regulatory approaches for gene editing are scientifically based and internationally harmonized in order to facilitate international trade.

In the years that followed, a growing number of governments, including Japan, Colombia, and the Philippines, have adopted similar policies. Announcements in countries including Russia, Kenya, and Indonesia have indicated a similar policy direction.

Against this backdrop, in September 2018, the European Court of Justice conducted a legal review of the applicability to gene-editing of the 2001 EU Directive regulating GM crops. The Advocate General appointed to advise the Court issued a statement concluding that because the products of gene editing contained no foreign DNA and could also have been developed through conventional breeding techniques, they posed a similar risk to conventional varieties and so should not be regulated in the same way as GM varieties. This position was supported by several Member States and EU Institutions. However, the final ruling of the court overruled the Advocate General’s position, and as a result, gene-edited products are considered GM in the EU at present.

The ruling produced a firestorm. It was supported by several NGOs but was harshly criticized by many groups, including EU Member States, National and EU Science Academies, trade and industry groups, and the Scientific Advisers to the European Commission. All these groups argue that the ruling was based on a legal interpretation of legislation written over twenty years ago and that it did not take into account scientific advances. They argued it was neither science nor risk-based, posed unjustified trade barriers audemars piguet replica, and could not be implemented for imported goods. In response to this broad-based backlash, in November 2019, the EU Council formally requested the European Commission to review the situation and propose changes to the law if needed.

The EU Council is currently scheduled to address the European Commissions proposed changes in the spring of 2021.

The goal is harmonized regulatory with all regulatory guidelines in all jurisdictions. It is our belief that, over the next two to three years, the Cibus gene editing technology will be uniformly confirmed as non-GM by the world’s regulatory agencies. That is what the science supports, and consequently, so do we.

In the next 30 years, the world’s farmers have a significant challenge ahead of them: feed an additional two billion people, all while adapting to climate change and little arable land. New advances in gene editing can enable the agricultural community to meet those challenges, but its deployment has been slowed by a number of misconceptions about how this technology works.

Like many scientific advances before it, gene editing was bound to elicit both deep excitement and scrutiny because it presents an opportunity to change something we once considered permanent. These game-changing gene-editing advances in medicine show that our society’s stance on the field may be shifting. But it also shows the number of public misconceptions that we still must address in agriculture in order to meet the demands of a growing population and climate change.

MISCONCEPTION ONE: GENE EDITING IS NEW IN AGRICULTURE

Over the past 10,000 years, all agricultural progress to create better crops has involved gene editing. We just didn’t know it at first.

In nature, we see mutations in plant’s DNA driven by natural causes, helping crops evolve and adapt to surroundings. When the changes are desirable — such as producing more robust fruit — plant breeders can exploit that change and breed more of the crop with the “altered” DNA. You may recall the work of Gregor Mendel from an early biology classes — the Austrian monk who identified and formalized different plant breeding techniques.

It’s true that plant breeding has taken several digressions, most notably in GMO crops to speed development of a particular trait, such as resistance to insect pests. Scientists develop transgenic plants by inserting DNA from an unrelated organism to achieve a desired result in less time than past methods of breeding. These hybrids and varieties have come to dominate certain crops such as corn and soybeans, though some consumer and social media groups have shown concern that introducing foreign genes into a plant might come with unintended consequences. As a result, there has been strong desire to return to plant breeding techniques that do not incorporate foreign genes.

MISCONCEPTION TWO: ALL GENE EDITING IS CLASSIFIED AS ‘GMO’

In some applications, gene editing does involve introducing foreign DNA into a plant’s genome. But this approach is just a small subset of the incredibly broad gene-editing field. Another subset — precision gene editing — does not involve integrating any foreign genetic material at any stage of breeding a new plant.

With our more comprehensive understanding of genetics, paired with new cutting-edge technologies like DNA cutters (e.g., CRISPRs) and oligonucleotides (e.g., GRONs), we are now able to edit a plant’s DNA at a very specific point. Scientists can now identify and edit the exact part of the genome that would be changed in nature to create the optimized crop, using a mix of clever organic chemistry and new tools. This approach has proven itself in the lab, the greenhouse and even the field — creating crops that are indistinguishable from those found in nature.

Had such tools been available 40 years ago, it’s doubtful that GMOs would have ever taken off. Precision gene editing accomplishes the same objective, but without chance and without the insertion of any foreign DNA.

MISCONCEPTION THREE: EDITING IN A LAB IS STILL CONCERNING

Even without introduction of foreign genetic material, some feel gene editing should be treated the same as GMO because the edits occur in a lab. But I’m here to tell you that eliminating the lab from the production of crops is simply not practicable, especially given the dramatic need we face for feeding our growing population. This standard would even eliminate many food crops produced by traditional plant breeding. Nearly all the potatoes we eat, for instance, are grown from seed that has gone through an essential “clean-up” in labs, during which technicians use tissue culture to get rid of viruses and bacteria.

Similarly, there are the questions of the so-called “escapes:” edits gone wrong that escape the lab and wreak havoc. Outside of science fiction, these outcomes are all-but-impossible. Edits are performed at the level of a single cell, and it takes extraordinary care to nurture these edited cells beyond microscopic form, since none are able to survive on their own. All cells undergo screening and gene sequencing to ensure that only those with the specific desired changes are taken to the greenhouse. With these precautions, we can control exactly which plants ultimately leave the lab.

MISCONCEPTION FOUR: GENE EDITING WILL ONLY HELP ‘BIG AG’

Finally, there are fears that gene editing will increase the stranglehold that agricultural giants exercise over food production. In fact, the exact opposite is true — the speed, ease, and low cost of the technology levels the agricultural playing field. The new technology can produce new traits ten times faster, at one tenth the cost of transgenic approaches, with a more efficient regulatory path. This removes the need to spend $100 million to develop a new trait, and, in turn, reduces the barrier to entry for a host of smaller companies attempting to improve the world’s crops.

The public and policymakers are right to be cautious about any new technology — gene editing, or otherwise. However, gene editing offers the chance to accomplish what we once thought of as impossible. We cannot have our own misconceptions bar us from enacting real change, especially when feeding an impending 2 billion lives is at stake.

“Congratulations to my former boss from the Salk Institute, Detlef Weigel, on receiving the prestigious 2020 Novozymes Prize. He was very influential in my early career and his insights into the effects of climate change on the European continent are important. See the article below for a look at how Dr. Weigel believes gene editing can be a significant benefit to this area of the world.” — Greg Gocal

The trajectory of global climate change will strongly affect the ability of plants to grow. However, contrary to what one might think, the plants in the hottest regions will not always be those immediately hit hardest.

“Since it will become even drier around the Mediterranean, one might think that the Mediterranean plant populations are the ones that are most at risk. But it turns out that plants in central Europe may be at greater risk, because they basically have no genetic toolkit to deal with drought. Since evolution cannot catch up, we must consider using genome editing to help plants to adapt faster. Otherwise they can become extinct,” says Detlef Weigel, Professor and Director, Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany.

Detlef Weigel has studied plant development and adaptation for three decades. His outstanding research has led not only to fundamental understanding of the genetic structure of plants but also to technological contributions that have had major impact on the entire field of plant biotechnology. His work includes the use of genomics technologies to study the model plant Arabidopsis thaliana, which has led to detailed understanding of the variation in plant genomes, with great potential to help to prevent diseases and increase crop yields.

In recognition of the outstanding research he has undertaken during his entire research career, the 2020 Novozymes Prize is being awarded to Detlef Weigel. The Prize is awarded to recognize outstanding research or technology contributions that benefit the development of biotechnological science for innovative solutions. The Prize is accompanied by DKK 3 million and is awarded by the Novo Nordisk Foundation.

Bernard Henrissat, Chair of the Committee on the Novozymes Prize, says: “Detlef Weigel is an extremely high-calibre, imaginative and enthusiastic scientist. He achieves excellence through the clarity of his thinking, extensive literature analysis to ensure that he approaches each topic in a scholarly fashion and excellent execution of his projects. The work of Detlef Weigel has driven forward the plant field and generated outstanding research contributions that have benefitted the development of innovative biotechnological solutions for breeding improved crops and feeding the world in the future.”

Biotechnological impact

An early achievement of Detlef Weigel was demonstrating that the LEAFY gene on its own can induce flower formation in Arabidopsis thaliana. However, while fascinating for basic research, the biotechnological interest of this discovery was at first limited, because this plant is just a small weed that grows on fields, along railroad tracks and at roadsides. The breakthrough came when Detlef Weigel was joined by a Swedish postdoctoral fellow, Ove Nilsson. Together, they made the remarkable discovery that the LEAFY gene has the same power to turn leafy shoots into flowers in aspen trees. Very differently from Arabidopsis thaliana, these plants typically make their first flowers only after 10 years, and plant breeders that want to cross different varieties with each other have to be very, very patient. With the LEAFY gene, they could reduce the onset of flowering to a few months. This was the first demonstration that genes from Arabidopsis thaliana, which has no agronomic or commercial value, could be used directly to change very different plants in a meaningful way – justifying investments both by established crop-breeding companies and by startups in using Arabidopsis thaliana as a powerful tool for biotechnological discoveries.

“The biotechnology field has relied heavily on the type of tools and approaches Detlef Weigel has pioneered. He is in all respects a very worthy recipient of the 2020 Novozymes Prize,” says Bernard Henrissat.

“Plants need help”

Arabidopsis thaliana has also formed the basis for Detlef Weigel’s recent work on how plants react to climate change. According to Detlef Weigel, plants in central Europe basically have no genetic toolkit to cope with extended drought, whereas the plants in the Mediterranean are already well equipped to deal with drought. Similar considerations almost certainly apply to crops, and this apparent danger has led the Intergovernmental Panel on Climate Change to specifically mention the potential of modern breeding technology and genome editing to help plants to adapt faster to global change.

Detlef Weigel says: “Evolution may not work rapidly enough to save these plants, but we are fortunate since we now have genomic technologies that give these plants a head start. Just as genome editing is revolutionizing medicine and animal breeding, it is a revolutionary technology for plants. Of course, our first priority must be to stop climate change – another area in which genome-edited plants can play an important role, by permanently removing carbon dioxide from the atmosphere.”

The 2020 Novozymes Prize comes as a great surprise to Detlef Weigel.

“Only a few people think of me as a biotechnologist first, so I feel doubly honoured that this was seen as an important contribution to biotechnology. Even though I will be the one who will be honoured, it is really for my team and the efforts of many amazing people with whom I have worked over the years. I would like to thank all of them in accepting this Prize.”

Prize ceremony

Detlef Weigel will officially receive the 2020 Novozymes Prize at a prize ceremony on 27 March in Bagsværd, Denmark.

About Detlef Weigel

• 2019 Barbara McClintock Prize for Plant Genetics and Genome Studies
• 2016 Genetics Society of America Medal
• 2015 Mendel Medal of the German National Academy of Sciences Leopoldina
• 2010 Foreign Member, Royal Society of London
• 2010 Otto Bayer Award of the Bayer Foundations
• 2009 Member, United States National Academy of Sciences
• 2001 Director, Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany
• 2003 Adjunct Professor, Plant Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
• 1994 National Science Foundation Young Investigator Award
• 1988 PhD in Genetics, Max Planck Institute of Developmental Biology and Eberhard Karls University of Tübingen, Germany
  

  About the Novozymes Prize

  The Prize is awarded to recognize a pioneering research effort or a technological contribution that promotes the development of biotechnology science to generate innovative solutions. The Prize is accompanied by DKK 3 million: DKK 2.5 million for the Prize recipient’s research and a personal award of DKK 0.5 million.

  The Prize is awarded for a predominantly European contribution. Prize recipients must be employed at a public or non-profit research institution in a European country. They can have any nationality. The Committee on the Novozymes Prize awards the Prize on behalf of the Novo Nordisk Foundation based on nominations received. Anyone may nominate a candidate for the Prize.

  About the Max Planck Society and the Max Planck Institute for Developmental Biology

  The Max Planck Society is Germany’s most successful research organization. Since its establishment in 1948, no fewer than 18 Nobel laureates have emerged from the ranks of its scientists, putting it on a par with the best and most prestigious research institutions worldwide. The more than 15,000 publications each year in internationally renowned scientific journals are proof of the outstanding research work conducted at Max Planck Institutes – and many of those articles are among the most frequently cited publications in the relevant field. The Max Planck Institute for Developmental Biology studies fundamental aspects of microbial, plant and animal biology both in the laboratory and in natural settings. To this end, it makes use of approaches that range from biochemistry and cell and developmental biology to evolutionary and ecological genetics, functional genomics and computational biology.

  Further information

  Christian Mostrup, Senior Press Officer, Novo Nordisk Foundation, cims@novo.dk, +45 3067 4805

  The 2020 Novozymes Prize is being awarded to Professor Detlef Weigel (photo) for his outstanding research contributions that have led to groundbreaking new knowledge of the genetic structure of plants. His work has had major impact on developing innovative biotechnological solutions for crop improvement and understanding how plants adapt to the environment. The Novo Nordisk Foundation awards the Prize, which is accompanied by DKK 3 million.