Government’s analysis, assessment and research activities Utilisation of New Genome Editing Techniques in Finland Nina Wessberg, Santtu Lehtinen, Anneli Ritala, Suvi T. Häkkinen, VTT Johanna Vilkki, Alan H. Schulman, LUKE Jussi Laine, Satu Korhonen, Demos Helsinki P U B L I C AT I O N S O F T H E G O V E R N M E N T ’ S A N A LY S I S , A S S E S S M E N T A N D R E S E A R C H A C T I V I T I E S 2 0 2 1 : 3 9 tietokayttoon.fi /en Utilisation of New Genome Editing Techniques in Finland Nina Wessberg, Santtu Lehtinen, Anneli Ritala, Suvi T. Häkkinen, VTT Johanna Vilkki, Alan H. Schulman, LUKE Jussi Laine, Satu Korhonen, Demos Helsinki Prime Minister’s Office Helsinki 2021 Publications of the Government´s analysis, assessment and research activities 2021:39 Prime Minister’s Office © 2021 Authors and Prime Minister’s Office ISBN pdf: 978-952-383-142-1 ISSN pdf: 2342-6799 Layout: Government Administration Department, Publications Helsinki 2021 Finland Publication distribution Institutional Repository for the Government of Finland Valto julkaisut.valtioneuvosto.fi Publication sale Online bookstore of the Finnish Government vnjulkaisumyynti.fi https://julkaisut.valtioneuvosto.fi/ https://vnjulkaisumyynti.fi/ Description sheet 21 May 2021 Utilisation of New Genome Editing Techniques in Finland Publications of the Government´s analysis, assessment and research activities 2021:39 Publisher Prime Minister’s Office Authors Nina Wessberg, Santtu Lehtinen, Anneli Ritala, Suvi T. Häkkinen, Johanna Vilkki, Alan Schulman, Jussi Laine, Satu Korhonen Group Author VTT, LUKE, Demos Helsinki Language English Pages 98 Abstract The objective of this report is to produce information on the current state and future of the new genome editing techniques. The report material was collected from the literature, supported by expert interviews and business surveys. In addition, two stakeholder meetings were organised. Furthermore, statistics and the scenario method were utilised in the project. The new genome editing techniques enable one to add, remove or edit the desired qualities of an organism very accurately and in a targeted way. In Finland, these techniques are mainly applied in basic research on plants and in animal physiology, as well as in medical research and development to produce test animal and cell models. Genome editing techniques could be applied for improving the climate resilience of plants as growing conditions become altered by climate change. In addition to medical trials, the techniques enable development of gene therapeutic treatments. In animal breeding, the expectations centre on improving health and wellbeing of animals. The development of applications is hindered by the interpretation of European legislation that equates the new genome editing techniques with genetic modification. This keeps the costs of the required risk evaluation high. In addition, the consumer stance towards gene modification is negative, which means that the market of genome edited products is viewed as unstable. Provision This publication is part of the implementation of the Government Plan for Analysis, Assessment and Research. (tietokayttoon.fi) The content is the responsibility of the producers of the information and does not necessarily represent the view of the Government. Keywords research, research activities, CRISPR-Cas9, genome editing, gene editing, scenario ISBN PDF 978-952-383-142-1 ISSN PDF 2342-6799 URN address http://urn.fi/URN:ISBN:978-952-383-142-1 http:// Kuvailulehti 21.5.2021 Uusien genominmuokkaustekniikoiden hyödyntäminen Suomessa Valtioneuvoston selvitys- ja tutkimustoiminnan julkaisusarja 2021:39 Julkaisija Valtioneuvoston kanslia Tekijä/t Nina Wessberg, Santtu Lehtinen, Anneli Ritala, Suvi T. Häkkinen, Johanna Vilkki, Alan Schulman, Jussi Laine, Satu Korhonen Yhteisötekijä VTT, LUKE, Demos Helsinki Kieli englanti Sivumäärä 98 Tiivistelmä Tämän selvityksen tarkoitus on tuottaa tietoa uusien genominmuokkaustekniikoiden nykytilasta ja tulevaisuudesta. Selvityksen aineisto kerättiin kirjallisuudesta, asiantuntijahaastatteluin sekä yrityskyselyn avulla. Hankkeessa järjestettiin kaksi sidosryhmätilaisuutta. Lisäksi hyödynnettiin tilastoaineistoa ja skenaariomenetelmää. Uusilla genominmuokkaustekniikoilla on mahdollista lisätä, poistaa tai muokata organismin haluttuja ominaisuuksia hyvin tarkasti ja kohdennetusti. Niitä sovelletaan tällä hetkellä Suomessa pääasiassa kasvintutkimuksen ja eläinfysiologian perustutkimuksessa sekä lääketieteellisessä tutkimuksessa ja kehityksessä tuottamalla geenieditoinnilla koe-eläin- ja solumalleja. Uusia genominmuokkaustekniikoita voitaisiin soveltaa mm.kasvien säänkestävyyden parantamiseen ilmastonmuutoksen muuttamissa kasvuolosuhteissa. Lääketieteessä lääketutkimuksen lisäksi uudet genominmuokkaustekniikat mahdollistavat geeniterapeuttisten hoitojen kehittämisen. Eläinjalostuksessa toiveet kohdistuvat eläinten terveyden hyvinvoinnin parantamiseen. Sovellusten tuottamisen kasvua estävät eurooppalainen lainsäädännön tulkinta, joka rinnastaa uudet genominmuokkaustekniikat geenimuunteluun. Tämä pitää vaaditun riskinarvioinnin kustannukset korkeina. Lisäksi kuluttajien asenne geenimuuntelua kohtaan on negatiivinen, jolloin myös genominmuokattujen tuotteiden markkinat koeteen epävarmoiksi. Klausuuli Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa. (tietokayttoon.fi) Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä. Asiasanat tutkimus, tutkimustoiminta, CRISPR-Cas9, genominmuokkaus, geenieditointi, skenaario ISBN PDF 978-952-383-142-1 ISSN PDF 2342-6799 Julkaisun osoite http://urn.fi/URN:ISBN:978-952-383-142-1 http:// Presentationsblad 21.5.2021 Nyttjandet av nya genomredigeringstekniker i Finland Publikationsserie för statsrådets utrednings- och forskningsverksamhet 2021:39 Utgivare Statsrådets kansli Författare Nina Wessberg, Santtu Lehtinen, Anneli Ritala, Suvi T. Häkkinen, Johanna Vilkki, Alan Schulman, Jussi Laine, Satu Korhonen Utarbetad av VTT, LUKE, Demos Helsinki Språk engelska Sidantal 98 Referat Syftet med utredningen är att producera information om nuläget och framtiden för nya genomredigeringstekniker. Materialet samlades in från litteraturen, genom intervjuer med experter och med en företagsundersökning. I projektet ordnades två möten för intressenter. Dessutom användes statistiskt material och scenariometoden. Med nya genomredigeringstekniker kan man göra riktade förändringar med hög precision hos en organism genom att lägga till, ta bort eller förändra specifika egenskaper hos organismen. I Finland tillämpas teknikerna främst inom växtforskning, grundforskning i djurfysiologi samt medicinsk forskning och utveckling där man producerar försöksdjurs- och cellmodeller genom geneditering. Nya genomredigeringstekniker skulle kunna användas bland annat för att anpassa växter till de nya förhållandena som klimatförändringen medför. Inom den medicinska sektorn skapar teknikerna möjligheter för läkemedelsprövning och potential att utveckla genterapeutiska behandlingar. Inom husdjursaveln är målen inställda på att förbättra djurhälsan. Produktionen av tillämpningar fördröjs av tolkningen av den europeiska lagstiftningen, som jämställer nya genomredigeringstekniker med genmodifiering. Tolkningen innebär höga kostnader för riskbedömning. Dessutom har konsumenterna en negativ inställning till genmodifiering och därför anses marknaden för genomredigerade produkter osäker. Klausul Den här publikation är en del i genomförandet av statsrådets utrednings- och forskningsplan. (tietokayttoon.fi) De som producerar informationen ansvarar för innehållet i publikationen. Textinnehållet återspeglar inte nödvändigtvis statsrådets ståndpunkt Nyckelord forskning, forskningsverksamhet, CRISPR-Cas9, genomredigering, geneditering, scenario ISBN PDF 978-952-383-142-1 ISSN PDF 2342-6799 URN-adress http://urn.fi/URN:ISBN:978-952-383-142-1 http:// Table of Contents Foreword.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Glossary, Limitations and Applied Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1 Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 1.1 Objective, Publishers, and Report Content. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 1.2 Research Questions and Methods.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2 Theoretical Background.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 2.1 Societal Significance and Responsible Development of New Genome Editing Techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 2.2 Varied Applications of New Genome Editing Techniques.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 2.2.1 New Genome Editing Techniques as a Part of Agricultural Production and Plant Breeding.. . . . . 26 2.2.2 New Genome Editing Techniques as a Part of Animal Breeding.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 2.2.3 New Genome Editing Techniques as a Part of the Global Food System.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 2.2.4 New Genome Editing Techniques as a Part of Ecology.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 2.2.5 New Genome Editing Techniques as a Part of Medical Science.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 2.3 Legal Position of New Genome Editing Techniques in the EU and on a Global Level.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 2.3.1 International Regulation of New Genome Editing Techniques in Plant Breeding.. . . . . . . . . . . . . . . . . 31 2.3.2 Case Norway. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.3.3 The Stance of the Court of Justice of the European Union.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 2.3.4 Potential Consequences of the CJEU Ruling .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 3 Actors Utilising New Genome Editing Techniques in Finland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 3.1 Scientific Communities and Research Institutes.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 3.2 Government, Organisations and Foundations .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 3.3 Companies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 4 Plant Breeding and New Genome Editing Techniques.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 4.1 Current State.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 4.2 International Scope.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 4.3 Future: Threats and Possibilities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5 Animal Breeding and New Genome Editing Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.1 Current State.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.2 International Scope.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 5.3 Future: Threats and Possibilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 6 Medical Science and New Genome Editing Techniques.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 6.1 Current State.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 6.2 International Scope.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 6.3 Future: Threats and Possibilities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 7 Research and Education Requirements.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 8 Possibilities of New Genome Editing Techniques from the Perspectives of Finnish Business, Import, and Export .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 9 Development Paths of Genome Editing: Scenarios . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 9.1 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 9.2 Description of the Scenario Method.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 9.3 Scenarios.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 9.3.1 Futures Table.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 9.3.2 Just in Case.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 9.3.3 Growth from Sustainability.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 9.3.4 Data-Based Decision-Making.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 10 The Current State and Future of New Genome Editing Techniques.. . . . . . . . . . . . . . . . . . . . . . . 85 11 Conclusion.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Appendices.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 APPENDIX 1: Interview frame.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 APPENDIX 2: The Programme of the Opening Meeting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 APPENDIX 3: The Programme of the Stakeholder Workshop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Sources and Further Reading.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 8 Publications of the Government´s analysis, assessment and research activities 2021:39 F O R E W O R D Several representatives from the fields of research and business in plant breeding, animal breeding and medicine were interviewed for this report. In addition, a few representatives and board members of associations were interviewed. It should be noted that the research representatives were unanimous about the benefits of new genome editing techniques, and that on several occasions, these new techniques will even revolutionise development. These techniques enable us to significantly quicken and direct the creation of the correct variations. The only general negative stance against the utilisation of new genome editing techniques was expressed by the companies operating on the consumer interface and by representatives of organic producers. Representatives of consumer production fear that the products will not sell, while the representatives of organic producers reject the utilisation of genome editing at least in plant breeding for strictly ideological reasons. On a general level, our report also revealed that people do not know what genome editing is. At times, even the interviewed experts equated new genome editing techniques with gene manipulation. In addition, no one was able to explain the biological risk factors related to new genome editing techniques. The more evident, targeted risks are related to the misuse of techniques, such as terroristic purposes, or mixing the plants used in organic production with genome edited plants. Therefore, the rejection is not based on research information about the harms of genome editing techniques to people or to the environment. However, it can be said that new genome editing techniques are dividing the society into those who support genome editing, based on the familiarity with the basics of the said techniques, and those who oppose them without knowing what they are all about. Therefore, the most substantial lesson of this report, in my opinion, is that gene aspects, including genome editing and new genome editing techniques, should be taught to people as per the views of the experts interviewed in this report, especially during upper secondary education. This would increase knowledge, and people would attain a better ability to decide whether they are for or against new genome editing techniques. On behalf of the entire consortium, I would like to extend my deepest gratitude to all interviewees, the steering group of the project and to the researchers that were swept away by this fascinating topic. Nina Wessberg, Leader of the Project Consortium March 2021 9 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 G LO S S A RY, L I M I TAT I O N S A N D A P P L I E D A B B R E V I AT I O N S Abiotic stress Stress caused by environmental factors such as drought, heat, cold, light, and salinity. ALLEA The European Federation of Academies of Sciences and Humanities BTNK Advisory Board on Biotechnology under the Ministry of Social Affairs and Health Convention on Biological Diversity, CBD The secretariat of the UN Biodiversity Convention. Biodiversity refers to the richness of nature. Cartagena Protocol on Biosafety Biosafety protocol, a part of a larger UN Treaty that aims to ensure the environmentally safe use of gene technology. Cisgenesis Cisgenesis refers to a genome editing method, in which a new gene originates from the same or a cross-breedable species. CRISPR-Cas9 CRISPR-Cas9 is a defence system against viruses, originally found in bacteria. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) are DNA sequences that help bacteria to identify viruses that target them. These sequences function as memory in the defence system of the bacteria. Cas9 refers to CRISPR-associated protein 9, an enzyme that cleaves DNA, i.e., a nuclease. With the help of CRISPR-Cas9, editing can be performed in a targeted way on the desired region of the genome, on the gene sequence. The Cas9 nuclease is guided towards the specific, targeted strand of DNA with the help of a corresponding RNA sequence (guide RNA). Then, the Cas9 cleaves the target DNA part. The method is also known as genetic scissors. The cell attempts to repair the DNA cleavage and attach the DNA strands back together (non-homologous end joining, NHEJ). Therefore, insertions, i.e., additional nucleotides or deletions, or omitted nucleotides, can occur. Nucleotides can also be altered to match a desired model (homology-directed repair, HDR). These alterations typically cause a mutation in the target area. CRISPR-Cas9 is one of the new genome editing techniques. In addition, the CRISPR-Cas9 technique enables the addition of a gene to the cleaved DNA sequence, in which case this research project will also entail the terms gene transfer, genetically modified organism (GMO), genetically modified, and transgenic. 10 Publications of the Government´s analysis, assessment and research activities 2021:39 DNA, DNA Sequence Deoxyribonucleic acid is a polymer that encodes the organism’s genetic material, the genome. DNA consists of deoxyribose sugar, phosphoric acid, and nucleotides A(adenine), C(cytosine), G(guanine), and T(thymine). Furthermore, DNA sequence refers to the sequence of nucleotides. EPO Hormone Erythropoietin EPSO European Plant Science Organisation ETP European Technology Platform CJEU The Court of Justice of the European Union FAO Food and Agriculture Organisation of the United Nations FIMEA Finnish Medicines Agency Fimea Gene drive A gene drive is a natural event that has been utilised in genetic engineering. With the help of a gene drive, the desired genes can be transmitted in a sexually reproducing population so that the probability of the offspring inheriting the said genes is higher than the frequency in normal population (50 percent probability according to Mendal’s laws). Gene drives enable efficient genetic modifications of populations and even entire species with a very small number of modified individuals. Gene editing, GE The term gene editing is generally used as a synonym for new genome editing techniques, see new genome editing techniques. Gene transfer technique, GM technique Gene transfer techniques refer to all methods that transfer genetic material to the individual’s genomes. Crossbreeding, in which an organism is developed towards the desired outcome through artificial means as orchestrated by humans and therefore quickening evolution, is not considered as a gene transfer technique. 11 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 Genetic engineering Genetic engineering is a general term that refers to all methods that manage genetic material. These methods include GM techniques, gene transfer techniques, genome editing techniques, gene editing techniques, DNA techniques, RNA techniques, and cloning. The so-called classic mutagenesis techniques, such as irradiation and chemical treatment, are not considered to be genetic engineering. GTLK The Board for Gene Technology under the Ministry of Social Affairs and Health Gene therapy Gene therapy treats diseases caused by defective or missing genes in somatic cells, that is, in all types of cells with the exception of gametes and their stem cells. Genome editing Genome editing is a range of gene techniques that edit the genomes of an organism by adding, removing, changing, or replacing parts of the DNA. Several different genome editing techniques have been developed (see new mutagenesis techniques below). The most recognised new genome editing technique is called CRISPR-Cas9. It should be noted that in this research project, the following terms shall be used: gene transfer, genetically modified, GMO, genetically modified organism, transgenic organism when referring to transferring a new functioning gene, regulatory sequence, or a combination of several parts of a gene (recombinant) as a part of the genome editing process. Mutagenesis techniques In this research project, mutagenesis techniques have been divided into new and classic techniques. New mutagenesis techniques refer to genome editing techniques that enable for targeted, focused changes performed on the genomes. These techniques include, for example, CRISPR-Cas9 (see above), TALENs (transcription activator-like effector nuclease), and Zinc Finger Nuclease (ZFN). This research project applies the following choice of terminology: gene transfer, genetically modified, GMO, genetically modified organism, transgenic organism when referring to transferring a new functioning gene, regulatory sequence, or a combination of several parts of a gene (recombinant) as a part of the genome editing process. The so-called classic mutagenesis techniques encompass methods such as irradiation and chemical treatment. Genetically modified organism, GMO Organism created with the help of gene transfer techniques; a synonym for transgenic organism. 12 Publications of the Government´s analysis, assessment and research activities 2021:39 Genetic modification technique, GM technique A synonym for gene transfer technique New Plant Breeding Techniques, NPBTs See New Plant Breeding Techniques below. Nucleotide A building block of nucleic acid, i.e., DNA and RNA. Recombinant In this research, recombinant refers to a gene produced through a DNA- combination technique, which is transferred to the genomes of an organism. Furthermore, the gene can also be entirely synthetic, i.e., artificially constructed. RNA, RNA sequence Ribonucleic acid is a polymer that directs the synthesis of proteins according to its code. Ribonucleic acid consists of ribose sugar, phosphoric acid, and nucleotides A(adenine), C(cytosine), G(guanine) and U(uracil). RNA sequence refers to the sequence of nucleotides in the RNA. Transgenic organism, GMO A synonym for genetically modified organism. Somatic cells, somatic With the exception of gametes and their stem cells, all types of cells are defined as somatic cells. Synthetic genomes Synthetic genomes refer to chemically synthesised complete or nearly complete genomes. TALEN One of the new genome editing techniques, the transcription activator-like effector nucleases. New genome editing techniques The new genome editing techniques refer to methods, in which the genome is targeted and accurately edited. These new techniques include site-directed mutagenesis (through utilisation of directed nucleases to cleave targeted DNA (site‐directed nucleases type 1 and 2 and oligonucleotide‐directed mutagenesis)), cisgenesis, alteration of DNA methylation and synthetic genomes. In this research project, the following terminology have been applied: gene transfer, genetically modified, GMO, genetically modified organism, transgenic organism when referring to transferring a new functioning gene; regulatory sequence, or a combination of several parts of a gene (recombinant) as a part of the genome editing process. 13 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 New Plant Breeding Techniques, NPBTs This term is generally used as a synonym for new genome editing techniques. However, the concept is notably more comprehensive; for example, grafting or graftage into a genetically modified rootstock or with a genetically modified scion. Furthermore, many other methods are placed in this category. 14 Publications of the Government´s analysis, assessment and research activities 2021:39 1 Introduction New genome editing techniques enable for adding, removing, or editing the desired qualities of an organism accurately and in a focused way. For example, with CRISPR-Cas9 molecular or genetic “scissors”, nucleotides in DNA can be added, removed or altered in specifically identified parts of the genome. To illustrate, plants’ resistance to plant disea- ses have been improved with the help of molecular scissors, and currently, the technique is utilised in developing gluten-free wheat, among other things. By utilising genome infor- mation and new genome editing techniques, it is possible to develop even better treat- ment therapies for diseases caused by gene defects. New genome editing techniques have been rapidly developed in the past few years, even to a point where new innovations and techniques are created every month. The name ‘new genome editing techniques’ is, therefore, a bit misleading since new techniques are constantly being created. Therefore, it might be more accurate to discuss targeted genome editing when referring to genetic scissors and gene editing, and differentiate between them and non-targeted genome editing, such as gene transfers or creating mutations through irradiation or chemical treatment. Currently, genome editing is cheap and accurate. The number of biotechnological and similar companies as well as commercial applications that utilise genome editing has increased significantly. In fact, the market is considered to hold a great growth potential1. These new development paths and the new applications of existing technologies are raising remarkable questions from the perspective of the environment, society, and public health. The new genome editing techniques can, for example, edit nearly any part of a genome with a properly designed guide RNA sequence, which is a significant improvement from prior techniques. In addition, effective genome editing techniques have a significant role in the framework of synthetic biology, as thousands of variants can be generated quickly, therefore considerably speeding Design-Build-Test-Learn cycles. The development of accurate genome editing techniques will also improve the development 1 Brinegar, K. (2017) The commercialization of genome-editing technologies. Critical Reviews in Biotechnology 37:7. 15 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 of gene therapies. The defective genes can be repaired accurately with the new methods, thus creating efficient treatment options for diseases and illnesses that have been either completely untreatable, inefficiently treated, only symptomatically treated, or treatable but not curable. The Court of Justice of the European Union commented on the juridical position of the new genome editing techniques (also known as new mutagenesis techniques) in July 20182. The CJEU ruled that organisms generated through new mutagenesis techniques belong to the category of genetically modified organisms (GMO). The GMO definitions are based on directives 90/220/EEC ja 90/219/EEC, decreed almost 30 years ago, and which, with the exception of the definitions, have been subsequently renewed (directives 2001/18/EC3 and 2009/41/EC4). Currently, only the so-called traditional mutagenesis techniques, such as irradiation and chemical treatment, which have a long history of safe use in plant breeding, are left outside the regulatory scope of the directive. This can create challenges, because for one, most organisms generated through the traditional and new mutagenesis techniques cannot be distinguished by any of the existing analysis methods. This specifically applies to the removal or addition of individual nucleotides. Moreover, if new mutagenesis techniques are used as gene transfer tools to transfer a gene to a genome, the techniques are regulated by directive 2001/18/EC. If the organism in question is a food or a feed, it is regulated in accordance with the regulation EC No 1829/2003. Furthermore, delivering GMO into the market is a long and expensive process. The research and plant breeding communities especially are of the opinion that the 2001/18 GMO directive of the EU has become obsolete and is still based on the level of technologies from decades ago. The adherence to the GMO legislation makes bringing GM products to the market very challenging and expensive. Now, the ruling of the Court Justice of the European Union places the products that could utilise new genome editing techniques under this same regulation, making introduction of such products to the European markets nearly impossible. During Finland’s presidency of the Council of the European Union in 2019, the Council’s decision to request the European Commission for a report on the current state of new 2 http://curia.europa.eu/juris/document/document. jsf?text=&docid=204387&pageIndex=0&doclang=EN&mode=lst&dir=&occ=first&part=1&cid=6972558 3 Directive 2001/18/EC of the European Parliament and of the Council on the Deliberate Release Into the Environment of Genetically Modified Organisms and Repealing Council Directive 90/220/EEC. 4 Directive 2009/41/EC of the European Parliament and of the Council on the Contained Use of Genetically Modified Micro-Organisms. http://curia.europa.eu/juris/document/document.jsf?text=&docid=204387&pageIndex=0&doclang=EN&mode=lst&dir=&occ=first&part=1&cid=6972558 http://curia.europa.eu/juris/document/document.jsf?text=&docid=204387&pageIndex=0&doclang=EN&mode=lst&dir=&occ=first&part=1&cid=6972558 16 Publications of the Government´s analysis, assessment and research activities 2021:39 mutagenesis techniques and the regulatory development needs was accepted. The regulatory demand for new genome editing techniques in relation to the current EU regulation on gene engineering and international environmental agreements is, therefore, a very topical question. In Finland, genetically modified organisms are regulated through the Gene Technology Act (377/1995), Medicines Act (395/1987) and Seed Act (600/2019), as well as by at least 15 other national laws and acts. Furthermore, the applicability of the new techniques is distributed under several different ministries. For example, the Ministry of Social Affairs and Health is preparing a new genome act, which proposes to secure the genetic data of an individual, containing data on possible mutations among other things. Genome editing of human gametes, however, is not ethically permitted in the EU, or anywhere else in the world. Therefore, this topic will not be discussed in this report. Regardless, when the intent is to develop treatments and therapeutic technologies that target somatic cells (i.e., cells excluding gametes) in genetic diseases, these aspects should also be considered. The objective of the genome act under preparation at the Ministry of Social Affairs and Health is to create common ethical principles for handling human genome data. Furthermore, the act is meant to form a basis for a genome centre under the Finnish Institute for Health and Welfare (THL). The centre is meant to function as a keeper for the genome data collected from humans and as a centre of excellence. The centre does not, however, manage genome data and expertise related to other organisms, such as plants and animals. The Government’s proposal for a genome centre on human health and genome data management is proposed to be presented to the Parliament in autumn 2021. 5 6 The differences between countries regarding the regulation of new mutagenesis techniques complicate the situation even further. For example, in the United States and Brazil, mutants generated through new mutagenesis techniques are not considered to belong under genetic engineering regulation, and this could significantly complicate international trade. From the Finnish perspective, there is a great call for more information on the state of new genome editing techniques not only from the perspective of the Finnish regulation, but also for the support of trade politics and regulation development. Information on the current and future needs and applications of the new technologies is required to form Finland’s stance towards the regulation of new genome editing techniques. 5 https://www.eduskunta.fi/FI/naineduskuntatoimii/kirjasto/aineistot/kotimainen_oikeus/LATI/Sivut/ genomilaki.aspx 6 VNK 2020. Innovaatiomyönteinen sääntely: Nykytila ja hyvät käytännöt. Valtioneuvoston selvitys- ja tutkimustoiminnan julkaisusarja 2020:27 17 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 Both the EU Commission and the UN Convention on Biological Diversity (CBD) are currently in the process of collecting background information on the utilisation and future applications of new genome editing techniques in the EU member states and CBD parties. In this report, the Finnish authorities and other stakeholders are offered background information on Finland’s situation, specifically. Information on the current and future needs and applications of new genome editing techniques is required to form Finland’s stance towards potential change proposals regarding regulations. This report secures the aforementioned demand for information. 1.1 Objective, Publishers, and Report Content In this research project, the current content and extent of utilisation of genome editing techniques is clarified. The report includes research, product developmental and commercial utilisation. New business opportunities are identified through the needs of different fields and scenario analysis. It is significant to clarify, for various sectors, the different possibilities and demands for the utilisation of the techniques. In addition to the needs of basic research, agriculture, biotechnology, medicine, and environmental sectors, this report will acknowledge the potential import demand of organisms and derived products generated through new genome editing techniques from third countries, as well as Finland’s export opportunities for the same. In the research project here reported, an up-to-date understanding of the economic and public health significance of new genome editing techniques was formed. Furthermore, the health and environmental threats connected to genome editing are identified in the report, and the preparation demand of authorities connected to the said operations has been evaluated. The primary objective of the project was to clarify the current and future needs and applications of genome editing techniques. Authorities will be able to utilise this information in their decisions on potential changes regarding regulations. Moreover, the report has established the societal and economic perspectives on genome editing techniques . Furthermore, the project clarified the business models enabled by genome editing techniques, as well as the realistic threats and opportunities connected to them. This report also assists in evaluating the impact of regulating genome editing techniques in different sectors, and therefore includes perspectives of economic impact, innovation, import, export, authorities’ tasks and resources, the opinions of citizens, producers and other actors, and the impact on the SME sector and food production, medical use. Furthermore, when discussing agriculture, a specific question is raised by the organic sector’s GMO ban. The research questions are presented based on the respective sub- projects in section 3. 18 Publications of the Government´s analysis, assessment and research activities 2021:39 The research project was carried out by VTT Technical Research Centre of Finland (VTT), Natural Resources Institute Finland (LUKE) and Demos Helsinki. VTT oversaw the execution of the project in its entirety, as well as the writing of this report. The principal investigator from VTT was Nina Wessberg. Santtu Lehtinen was responsible for the theoretical background, and they also participated in constructing the scenarios. Statistic material review was the responsibility of Mika Naumanen, while Anneli Ritala and Suvi T. Häkkinen provided their expertise on plant biotechnology. Johanna Vilkki and Alan Schulman from LUKE offered their expertise in genomics and respectively in animal and plant breeding. In addition, Jaana Peippo from LUKE also participated in conducting the interviews for the project. Demos Helsinki was responsible for the interaction with stakeholders in the project, as well as for the construction of the scenarios. From Demos Helsinki, Chris Rowley (transferred to other tasks from the project at the end of 2020), Satu Korhonen and Jussi Laine participated in the project. In this report, the current state of genome editing, international scope and future are described from the perspectives of plant breeding, animal breeding and medical science. Business opportunities and realistic threats are included in the review. 1.2 Research Questions and Methods The research project sought answers for questions related to three different aspects: 1. CURRENT STATE: the current state of genome editing techniques in Finland by sector with a needs assessment y To what extent are the new genome editing techniques currently utilised in Finland in basic research and in the agricultural, biotechnology, medical, and environment sectors? y For what purposes are the sectors currently implementing the new techniques? What kind of future needs can these sectors identify? y Do the aforementioned sectors have the ability and resources to utilise the said techniques on their own? If not, what kind of impediments are there? y How are the current use and potential future needs divided between the research and business sectors, as well as inside the said sectors? (basic research vs. applied research, SMEs vs large enterprises) 19 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 2. INTERNATIONAL SCOPE: Importing and exporting genome editing technique applications & international cooperation y Is the potential use/need based on importing? If yes: y What kind of applications are in question? Are the applications organisms or products generated through new genome editing techniques? y Which countries are likely to export such applications? y What is/could be the potential volume of import? y Do the different sectors have the need to import organisms generated with new genome editing techniques, products created through the said techniques, or innovations related to the techniques? If yes, to where would the importing activities be directed? y What kind of international cooperation is involved with the techiques’ use? 3. FUTURE, THREATS AND POSSIBILITIES: the impact and future development of utilising genome editing techniques y To which direction do the sectors anticipate the new genome editing techniques to develop, during the next ten years in Finland and overseas? What is the economic significance of the techniques these sectors perceive? y What kind of impact will the new genome editing techniques have on public health (impact of medication, vaccinations, gene therapy products or food)? y What kinds of novel, realistic biothreats are connected to different applications of new genome editing techniques in each sector? To which of these threats the authorities should be specially prepared for in the opinion of the sectors? y Is the use/non-use of these techniques connected to the national preparation for other types of threats (e.g., climate change, food security)? The answers for the research questions were mainly reached through interviews, which were executed as theme interviews. This means that the topic discussion with the interviewee followed a prepared frame of questions (see appendix 1). The frame acknowledged and included all research questions. The interviews were recorded and transcribed for analysis. The interviews were carried out through remote connections due to the assembly and travel restrictions caused by COVID-19. The total number of interviews conducted for this research was 49. One interview took about 30 to 60 minutes. The numbers of interviewees were distributed amoung 20 Publications of the Government´s analysis, assessment and research activities 2021:39 the sectors as follows: 17 research, 16 companies, six associations, six authorities or government, three funding and one from education. The interviewees were chosen based on actor analysis, during which the key actors that utilise and develop new genome editing in Finland and overseas were identified. Actor analysis was complemented by the so-called snowball method, which means that each interviewee was requested to name potential additional participants. The interviewees were continued until repetition of the information gained from the interviews was identified. Therefore, reliably comprehensive data collection was achieved. Actors connected to internationality and business were identified through a survey commissioned from Taloustutkimus Ltd. The survey measured the utilisation level of new genome editing techniques in businesses, the development of utilisation, needs connected to importing, as well as export potential. The survey was specifically oriented towards companies working with y plants, cereals, crop plants, y animals, cattle, y meat and milk products and food processing y gene therapies and treatments y pharmaceuticals Demos Helsinki delivered a register that contained the contact information of 132 actors to Taloustutkimus. Taloustutkimus updated the delivered register with the descriptive information of the company (such as revenue, personnel) and complemented the register with another contact information register printed from Bisnode Selector business data base based on the same actor information (a minimum revenue of two million euros was set as a delimiter). The data collection was carried out by phone interviews during November 5th until November 27th, 2020. The average time for one interview was about 12 minutes. Until the deadline, a total of 44 representatives of 43 companies were interviewed. In addition, a literature review and two events that involved stakeholder groups were carried out in the project. These parts have been described in detail in the following subsections. The research material accumulated in the research project, including the interviews and workshop materials, were analysed, and worked into scenarios, which were then applied to outline the current and future needs and applications of new genome editing techniques (See Chapter 9, The Development of Genome Editing: The Scenarios). 21 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 Opening Meeting To launch the project, a discussion event was organised on June 16th, 2020. During the event, the contribution to the research plan and key questions was collected from the stakeholders. Furthermore, a preliminary overall assessment on the current state of genome editing was formed, and the start of the project was communicated to all stakeholders. The detailed programme of the event is presented in appendix 2. The following organisations participated in the event: From the ministries: y Ministry of Social Affairs and Health y Ministry of Economic Affairs and Employment y Ministry of Agriculture and Forestry From research organisations and universities: y University of Helsinki y University of Turku y Natural Resources Institute Finland LUKE y Folkhälsan Research Center y Technical Research Centre of Finland VTT From the private and third sectors: y Association of ProAgria Centres y The Finnish Medical Society Duodecim y Association of Cancer Patients in Finland y The Central Union of Agricultural Producers and Forest Owners (MTK) y Nordic FoodTech VC y Pharma Industry Finland y Faba Cooperative Corporation y VikingGenetics Finland y Boreal Plant Breeding Ltd. Stakeholder Event In stakeholder meeting on December 12th, 2020, the results of the interview and survey studies were presented and feedback provided. In addition, the various future prospects of new genome editing techniques were processed. The event started with an introduction to the research project and with opening remarks on the current state of the new genome editing techniques based on the interviews and surveys. Thereafter, 22 Publications of the Government´s analysis, assessment and research activities 2021:39 the participants split into groups to discuss the need, regulation, attitudes, and business prospects of new genome editing techniques. The discussions were led by the facilitators of the research project. The participants were divided into groups to clarify the new genome editing techniques’ future potential and challenges from the perspectives of: 1) business, 2) daily life, and 3) society in 2030. The workshop procedures were based on co-creation methods. The stakeholder event programme has been included in appendix 3. The following actors participated in the stakeholder workshop: From the public sector: y Business Finland y Finnish Food Safety Authority y Finnish Medicines Agency Fimea From research organisations and universities, project funding: y Natural Resources Institute Finland LUKE y University of Helsinki y Academy of Finland From the private sector and company representatives: y Finnish Bioindustries FIB y Faba Cooperative Corporation y Roal Ltd y The Central Union of Agricultural Producers and Forest Owners (MTK) y Finpom Ltd y Lallemand Plant Care y VikingGenetics y Immuno Diagnostic Ltd 23 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 2 Theoretical Background 2.1 Societal Significance and Responsible Development of New Genome Editing Techniques The new genome editing techniques have created revolutionary opportunities for a variety of applications in different fields: genome editing can be utilised, for example, in biological basic research, health care applications, plant breeding, and production of materials. One of the most significant applications could be in the field of health care. New genome editing techniques are applied to develop health care treatments and methods that can assist, for example, in better diagnosis, treatment, and even curing different hereditary diseases. For the food supply chain, new genome editing techniques are being applied to create tools to answer the challenges caused by climate change, food crisis, and population growth.7 The most popular genome editing technique is CRISPR-Cas9, developed in 2012. The application potential of the technique has expanded. To illustrate, in plant breeding, new genome editing techniques have enabled the generation of desired mutations in an accurate and efficient way, all the while reducing the time spent on the breeding process. Genome editing has quickly expanded to extensive use all around the world, and it is actively utilised in the development of various scientific and commercial applications in universities, research institutes, SMEs, start-ups, and large, multinational enterprises8. The market for products generated through new genome editing techniques is expected to grow from the current five billion dollars to over ten billion dollars by the year 20259. Consequently, the demand for a competent workforce in the field is expected to grow significantly10. The new genome editing techniques have seen a rapid geographical expansion and versatile possibilities develop in the research and development activities of many fields. For example, the utilisation of CRISPR-Cas9 is relatively straightforward, which means that 7 Linturi 2020, 9–10. 8 Martin et al. 2020, 219–220. 9 See for example Sumant Ugalmugle & Rupali Swain. “Gene Editing Market worth over $10bn by 2026”. Global Market Insights. October 1, 2020. [Accessed 17.2.2021] 10 Richard Gray, “Why gene editing could create so many jobs”. BBC. 15th October 2018. [Accessed 17.2.2021] https://www.gminsights.com/pressrelease/gene-editing-market https://www.bbc.com/worklife/article/20181003-why-gene-therapy-will-create-so-many-jobs https://www.bbc.com/worklife/article/20181003-why-gene-therapy-will-create-so-many-jobs 24 Publications of the Government´s analysis, assessment and research activities 2021:39 it can be considered a ready, ‘off-the-shelf’ technique11. In addition, the fairly affordable genome editing techniques and their application possibilities make CRISPR-Cas9 and similar techniques available for even more actors12. According to some estimates, there could be even 100 000 laboratories and nearly one million researchers working with CRISPR-Cas9 all over the world13. However, the relative ease of use and extensive distribution of CRISPR-Cas9 also increase the potential misuse risk. In fact, CRISPR-Cas9 has highlighted new risks connected to biosafety, which have been noted by actors such as the US Intelligence Community14. Responsible application of genome editing techniques, such as CRISPR-Cas9, requires the support of extensive and professional societal discussion on the objectives, potential and limits. The ethical, juridical, and societal impact of new genome editing technique utilisation have been heavily debated among the experts. However, it is crucial that in addition to the experts, a larger audience and different stakeholders also participate in the conversation and present their own views, questions, and concerns15. The public interest towards new genome editing techniques is based on the various potential – direct or indirect, positive, or negative – impacts of their utilisation on the wellbeing of humans, animals, and natural habitats. It is crucial to manage this impact through public debate and democratic processes16. There is a special demand for a socio-cultural debate on the broad societal acceptance of genome editing techniques. Several previous examples of extensive scientific and technological innovations, such as nuclear power or GMO products, indicate that scientific evidence alone is not sufficient to provide understanding of the benefits and risks of these innovations; it also requires diversified dialogue. The disputes and conflicts centred around GMO products, specifically, are a great indication that a risk is both a political and cultural phenomenon that cannot be comprehensively managed from a purely technical perspective17. 11 Nuffield Council on Bioethics Report 2016, 13,112–113. 12 Montenegro de Wit 2020. 13 Eric Niiler. “How Crispr could transform our food supply”. National Geographic, August 10 2018. [Accessed 17.2.2021] 14 James R. Clapper. “Statement for the Record, Worldwide Threat Assessment of the US Intelligence Community”. Senate Armed Services Committee. February 9, 2016. [Accessed 17.2.2021] 15 Bruce & Bruce 2019, 770–771. 16 Nuffield Council on Bioethics Report 2016, 21–22. 17 Jasanoff 2016, 89–90; Sarewitz 2015. https://www.nationalgeographic.com/environment/future-of-food/food-technology-gene-editing/ https://www.nationalgeographic.com/environment/future-of-food/food-technology-gene-editing/ https://www.dni.gov/files/documents/SASC_Unclassified_2016_ATA_SFR_FINAL.pdf https://www.dni.gov/files/documents/SASC_Unclassified_2016_ATA_SFR_FINAL.pdf 25 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 Furthermore, risk assessment should act as a base for a more extensive societal discussion on how and under which conditions the utilisation of new genome editing techniques would be acceptable. During the risk assessment, it would be beneficial to examine potential benefits and targeting in addition to potential disadvantages. Which potential benefits justify taking the risks? To which actors are the benefits and disadvantages focused on? Does the utilisation of new genome editing techniques benefit global justice, or do they cause inequality?18 On a general level, the public acceptance of the new genome editing techniques and other biotechnical and gene technological applications has not significantly changed during the past two decades. While most research communities adopt an enthusiastic attitude towards the potential of the new techniques, the greater audience is quite sceptical, especially towards genetically engineered foods, animals, and plants. However, the broad audience on the EU level has adopted quite a positive stance towards genetically engineered medical applications, such as new treatment methods19. New genome editing techniques have created revolutionary possibilities for science, health care, and the economy. However, currently, the public debate on genome editing is easily deteriorated to a two-sided debate on regulation, which places the safety and innovation values on opposite sides. One side proposes to create new possibilities to promote business and solve societal issues, while the other wants to ensure that the risks connected to the applications of new genome editing techniques are minimised as much as possible20. However, research conducted in Norway, for example, gives the impression that the discussion on new genome editing techniques is multifaceted, and not just a traditional black-and-white conflict. Although, in general, people portray that gene technology has its risks, many are still open and accept the utilisation of new genome editing techniques in battling climate change and reducing the use of pesticides, for example. Therefore, it is evident that the acceptance of genome editing is impacted by the objective of the technique, the benefits, and the beneficiaries21. Instead of the two-sided debate, there is a major need for a multi-voiced, data-based public debate, in which different genetic engineering methods and their impact could be differentiated from each other. Creating a debate such as this requires that the societal actors, the general audience, the scientists, and gene engineering applicators come together. 18 Biotekniikan neuvottelukunta 2018, 17–18. 19 Woźniak et al. 2021. 20 Habets et al. 2019, 22–23. 21 The Norwegian Biotechnology Advisory Board 2020. 26 Publications of the Government´s analysis, assessment and research activities 2021:39 2.2 Varied Applications of New Genome Editing Techniques 2.2.1 New Genome Editing Techniques as a Part of Agricultural Production and Plant Breeding Farmers and plant breeders have been altering plant genomes for millenia. The objective of breeding has been to improve humankind’s food security by developing crop production and resistance to plant diseases, for example. In addition, most crops utilised today have been generated by breeders judging and selecting individuals with desired traits from among variants carrying naturally occurring mutations, at a later stage mutations caused by chemical treatments or irradiation. These individuals are then utilised in plant breeding. The utilisation of the new genome editing techniques can be seen as a continuum from this tradition, and therefore, genome editing techniques are often called new plant breeding techniques (NPBTs). Depending on the perspective, new genome techniques can be also be seen as a more efficient and accurate extension of traditional breeding, or, alternatively, as a technical innovation that revolutionises the human–nature relationship22. One of the applications for the new genome editing techniques with the most potential is, in fact, plant breeding. Implementation of genome editing techniques offers new measures and tools for plant breeders to adapt crops to threats created by climate change, such as the increasingly variable weather and extreme climate events. Constant plant breeding is necessary to improve plants’ resistance to various plant diseases and pests. Plant breeding is also crucial to answering the increasing global demand for food, while existing food systems are faced with more and more pressure23. However, the complex juridical position of genome editing techniques complicated their application to agriculture and plant breeding in the EU. First and foremost, the legal complexity is connected to interpretation of new genome editing techniques with regard to EU genetic engineering legislation. While the previous gene transfer techniques and GMO products are clearly governed by the genetic engineering regulations (2001/18), the legislative status of the new genome editing techniques has raised significant interpretative disagreement. The difference between the previous gene transfer technique and genome editing is the fact that in gene transfer, a gene with material from a single or multiple foreign species is transferred to a cell. As a rule, in genome editing techniques, a gene inside a cell is targeted, after which part or parts of its code is edited without adding any foreign material to the genome. Supporters of genome editing techniques argue that the technique’s safety aspect resembles the traditional mutation breeding and previous 22 e.g. ALLEA 2020, 32–33. 23 e.g. Biotekniikan neuvottelukunta 2018, 16–17. 27 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 mutagenesis techniques, such as irradiation and chemical treatment, while still being considerably more accurate than these previous methods24. The decision by the Court of Justice of the European Union (CJEU) in summer 2018 commented on the legal position of new mutagenesis techniques, that is, on genome editing techniques. Based on the decision by the Court of Justice, organisms generated by new mutagenesis techniques, such as by genome editing, are governed by the genetic engineering directive 2001/18/EC25. 2.2.2 New Genome Editing Techniques as a Part of Animal Breeding According to the supporters of genetic engineering, breeding animals by use of genome editing would continue a long tradition of breeding, only in a more efficient and accurate way. However, when discussing animals, the application of the genome editing techniques encounters three challenges: the potential economic benefits, regulation of the technology, and the societal acceptance of the technology26. In theory, genome editing techniques could enable editing animal traits in a way that benefits both the animals and humans. Around the world, applying genome editing on livestock has been justified primarily with the well-being of the animals, because these techniques can, for example, improve the animals’ resistance to different diseases and conditions. With the help of new genome editing techniques, swine resistance to infectious diseases has been improved; these diseases cause considerable suffering to animals and significant financial losses to producers. Genome editing techniques also offer the opportunity to lessen painful procedures performed on animals: polled cattle developed with these techniques help to minimise the risks and side-effects connected to horns and their removal for both the animals and care givers. 27 Discussion on the use and acceptability of genome editing in animal breeding has so far stayed on the side lines, partially due to their difficult implementation in comparison to, for example, plant breeding. However, there is reason to ask about the ultimate objective of genome editing in animals. For example, is the animal’s improved resistance going to be utilised to place even a greater number of animals in the same location? Questions 24 Eduskunnan tulevaisuusvaliokunnan julkaisu 2/2018, 9–13; Biotekniikan neuvottelukunta 2018, 19. 25 Court of Justice of the European Union. PRESS RELEASE No 111/18. Luxembourg, 25 July 2018. [Accessed 18.3.2021] 26 Nuffield Council on Bioethics Report 2016, 58, 62–64. 27 Bruce 2017, 386–387. https://curia.europa.eu/jcms/upload/docs/application/pdf/2018-07/cp180111en.pdf https://curia.europa.eu/jcms/upload/docs/application/pdf/2018-07/cp180111en.pdf 28 Publications of the Government´s analysis, assessment and research activities 2021:39 regarding the application of genome editing are inevitably connected to broader questions regarding animal rights, well-being, and our industrial food systems.28 2.2.3 New Genome Editing Techniques as a Part of the Global Food System Currently, the biggest challenges facing global food systems are climate change, population growth, and global competition for different resources. The two biggest drivers for food demand are population number and income level. The population of the world is forecast to grow to around 10 billion by the year 2050, while growth in income level increases the demand especially for milk and animal products globally.29 To answer this increasing demand, the Food and Agriculture Organisation states that the global agricultural production should grow by 60–70 percent compared to the production level of 200730. Genome editing is considered as one tool to solve these challenges related to increasing food production. In this regard, it is beneficial to note that the models suggested to solve the global food problem are always dependent on the definition and presentation of tha problem. If genome editing is primarily utilised to further enhance agricultural production and the food industry, the global food problem tends to be defined primarily as a technological problem, and therefore, technological solutions are offered.31 However, several environment and non-government organisations are of the opinion that quantitatively, there is enough food produced in the world as it is, and therefore, the root of the food problem lies within the unfair global distribution of food. Thus, the technological solution of the problem easily bypasses the structural, political, and economic questions related to the food system functions. In addition, offering technological solutions often disregards questions on the ownership of the technology and who has the opportunity to utilise it. The sceptical non-government organisations have based their stance on the claim that the previous GM techniques applied on food production have been primarily utilised to promote the interests of food production systems driven by big enterprises. According to these non-government organisations, it 28 Anna Wilkinson. “Genome editing to improve farmed animal welfare. What’s not to like?” 19 Feb 2020. Nuffield Council on Bioethics. [Accessed 17.2.2021] 29 Tait-Burkard 2018, 1–2. 30 Alexandratos et al. 2012, 7. 31 Habets et al. 2019, 27; Bruce 2017, 394–395. https://www.nuffieldbioethics.org/blog/genome-editing-to-improve-farmed-animal-welfare-whats-not-to-like https://www.nuffieldbioethics.org/blog/genome-editing-to-improve-farmed-animal-welfare-whats-not-to-like 29 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 would be more beneficial to focus on reducing food waste and improving distribution than on enhancing food production.32 The supporters of genome editing techniques emphasise that while GMO cultivation focused on enhancing the intensive farming of large soy and corn fields, the new genome editing techniques are more focused on fulfilling the demands and wishes of the consumers and reducing the food waste. The benefits and simplicity of utilising genome editing techniques create opportunities for small and local businesses to participate in the market, while only the biggest, multinational enterprises can compete with GMO in the market. It is said that in addition to the better crops, the utilisation of genome editing techniques also gives a new method of developing products. This creates even healthier and more tempting products from the perspective of consumers. Therefore, utilisation of the new genome editing techniques is not only connected to enhancing the quantity or efficiency of food production; they can also be used to improve food quality, nutritional values, and other qualities.33 2.2.4 New Genome Editing Techniques as a Part of Ecology Humankind’s increasing ability to read and utilise genetic information changes the human-nature relationship. For instance, genetic information has been utilised in attempts to develop the resistance of humans, animals and plants to viruses and bacteria. New genome editing techniques can be utilised in, for example, generation of so-called gene drives. In the future, gene drives might be implemented in exterminating insects that spread various diseases, such as malaria, Zika virus disease, or dengue fever.34 Utilising genome editing in the production of gene drives to combat, for example, malaria, does encompass ecological and ethical dimensions on the level of ecosystems. Gene drive refers to a method that assists in spreading the gene edit quickly through the entire population. Therefore, gene drive enables downsizing or total extinction of different populations. The issue with utilising gene drives is the difficultly in carrying out risk evaluation with the current methods. Gene drive exposes living organisms to quick, extensive, and permanent ecological changes, whose impact is difficult to evaluate in advance. The possibility of being unable to revert the edited population back to its previous state has increased the risks of gene drives. To answer this issue, conditional gene 32 Montenegro de Wit 2020, 23–24; Nuffield Council on Bioethics Report 2016, 69–72. 33 Ashley Taylor. “Gene Editing Meets The Food Supply - The New World of Custom-Designed Crops”. July 29, 2019. Milken Institute Review. [Accessed 17.2.2021] 34 Nuffield Council on Bioethics Report 2016, 76–77,80–81; Linturi 2020, 22–23. https://www.milkenreview.org/articles/gene-editing-meets-the-food-supply 30 Publications of the Government´s analysis, assessment and research activities 2021:39 drive systems are currently in development. These conditional systems would better limit the impact on a population level.35 2.2.5 New Genome Editing Techniques as a Part of Medical Science In treatment methods based on genome editing, an entire gene is not transferred as in previous gene transfer techniques; instead, the DNA inside the gene is edited. The significant public health potential of new genome editing techniques is based on the assumption that on a theoretical level, a variety of different diseases could be treated with this new gene technique. 36 Genome editing techniques and ever more affordable gene-based diagnostics have brought in new possibilities to improve people’s health and wellbeing. The costs of sequencing a human genome have dropped from 100 million dollars to about a thousand dollars since 2001, which has enabled progressive more efficient utilisation of hereditary information for diagnostics or lifestyle recommendations, for example.37 Gene-based diagnostics, combined with genome editing, create new possibilities for a better diagnosis of various diseases and individual treatments, which in turn can assist in more efficient treatments or even cures for several severe diseases in the future. 38 When discussing medical genome editing in humans, it is essential to differentiate between genome editing on somatic cells and on gametes. Somatic editing impacts only the patient receiving the treatment and their cells, while editing the germline impacts gametes, which means that the changes will be inherited by the future generations, too. In health care, somatic editing has been applied to treatments of diseases such as HIV, haemophilia, and anaemia, while germline editing can be targeted to the development of naturally occurring resistance to infectious diseases.39 However, it should be noted that editing the genomes of a human embryo is prohibited in the European Union on the basis of the Western science community’s perspective and the EU Convention on Human Rights and Biomedicine.40 35 Biotekniikan neuvottelukunta 2018, 8,16; Wartiovaara 2017, 133–134. 36 Wartiovaara 2017, 130–133; Linturi 2020. 37 Halioua-Haubolda et al. 2017, 683–684. 38 Hirakawa 2020; Linturi 2020, 21–22. 39 Cavaliere 2019, 1–2; Max Planck Society 2017, 17. 40 The Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine. Convention on Human Rights and Biomedicine (ETS No 164) was opened for signature on 4 April 1997 in Oviedo (Spain). [Accessed 18.3.2021] https://www.coe.int/en/web/bioethics/oviedo-convention 31 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 2.3 Legal Position of New Genome Editing Techniques in the EU and on a Global Level 2.3.1 International Regulation of New Genome Editing Techniques in Plant Breeding The international framework for regulating genome editing is multifaceted, entailing several laws and commitments. Currently, the Cartagena Protocol on Biosafety is the primary international agreement regarding the topic, despite the fact that some of the members have not signed or approved the Protocol. The purpose of the Biosafety Protocol is to promote global biosafety and minimise the risks to biological diversity and public health, based on precautionary principle.41 In this section of the review, the focus is on the status of genome editing techniques in plant breeding. Most of the national and international legislation on genetic engineering does not directly refer to genome editing techniques, because the technology in question is new, and it is utilised in numerous different fields. In agriculture and plant breeding, biotechnical applications are often considered under GMO regulations in one way or another.42 The Cartagena Protocol uses the term Living Modified Organism (LMO), not GMO, and the question of whether gene-edited organisms are LMOs or not is controversial. In the EU and New Zealand, new plant varieties generated with genome editing techniques are governed by the existing GMO and biosafety legislation. Several members have applied and interpreted their existing GMO legislation in relation to the new genome editing techniques as well. The international and multifaceted regulation creates potential challenges to the global trade in food, plant varieties, and agricultural products generated through with the editing methods.43 The genetic engineering legislation of the EU is based on the precautionary principle, which proposes to prevent irreversible impacts on human health and the environment. The EU GMO directive 2001/18/EC regulates the marketing and deliberate propagation of genetically modified organisms in the environment. GM food and fodder, on the other hand, are governed by regulation (EC) 1829/2003. The products under the scope of GMO directives always require a risk assessment, which evaluates the direct and indirect impacts on the health of humans, animals, and the environment. The directive also includes the responsibility of monitoring, tracking, and recording the products.44 The 41 Max Planck Society 2017, 17. 42 Menz et al. 2020, 2. 43 Schmidt et al 2020, 1–2; Ishii & Araki 2017, 7–9. 44 Habets et al. 2019, 10. 32 Publications of the Government´s analysis, assessment and research activities 2021:39 approval process of GMO products in the EU is demanding. The average costs of the five- year process for the applicant are around 10–15 million euros per product.45 In South America, the regulation and interpretation of the legal position of the new genome editing techniques has been taken the farthest on a global level. To illustrate, in 2015, Argentina was the first country in the world to revise their GMO regulation to include new regulatory criteria for new plant breeding techniques, such as genome editing. The criteria help to define the status of new organisms, varieties, and products on a case-by-case basis. According to the criteria, varieties that have been bred using genome editing do not belong under the scope of biosafety legislation and GMO regulation, if the variety does not include foreign genetic material. The regulation is based on a consultation process for a specific product, which helps to predict both the duration and costs of the process.46 Based on the preliminary results and experiences from Argentina, the country’s new systems have assisted in the commercialisation of products (mainly food items) generated through genome editing. These products are developed by several SMEs, start-ups, and research institutes, which have become more numerous in plant breeding due to the new regulations. In addition, several businesses have specialised in generating specific traits and products.47 In the United States and Canada, it is completely possible to approve all foodstuffs generated through genome editing for market under the existing legislation.48 Canada, in particular, is considered a model country for final product regulation, as the legislation does not differentiate between different plant breeding techniques. The product-based legislation of Canada is seen as flexible, and it does enable agricultural products generated by genome editing to be approved without updating the legislation. In fact, all agricultural products in Canada are regulated through the same legislative framework regardless of their production techniqe. Regulation is based on case-specific review of the new qualities of the new products.49 China is the global leader in utilising genome editing techniques, as measured by investments, launches, and patents. Surprisingly, despite the immense support of the government, China does not have an official legislative approach to genome editing. On the other hand, Russia has deemed GMO illegal in all other activities besides basic 45 Menz et al. 2020, 2. 46 Ishii & Araki 2017, 47–48; Menz et al. 2020, 7. 47 See e.g. Whelan et al. 2020. 48 Menz et al. 2020, 4. 49 See e.g. Ellens et al. 2019. 33 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 research. However, the situation on applying new genome editing is undergoing change in Russia, because the government has directed significant investments to biotechnology, and especially to genome editing. In fact, Russia is expected to update its policy on genome editing methodology in the near future.50 Figure 1 portrays the various legislative interpretations of genome editing techniques around the world. Figure 1.  The legislative interpretation on new genome editing techniques in different countries. Source: Schmidt et al. 2020, 2. 2.3.2 Case Norway On a global level, genome editing and new plant breeding techniques create a new challenge for current legislation, which is based on GMO products for the most part. One major question in the EU and all around the world is: ‘should new genome editing 50 Menz et al. 2020, 12. 34 Publications of the Government´s analysis, assessment and research activities 2021:39 techniques be regulated under the GMO framework or by other means?’ For this reason, the valuable trading partners of the EU, such as Switzerland, Norway, and Great Britain, are currently considering renewing the legislation on new genome editing techniques. One especially intriguing conversation on regulating and monitoring genome editing techniques is taking place in Norway.51 Among the Nordic countries, Norway clearly has the most non-conventional legislation on gene technology. The Norwegian legislation is based not only on comprehensive risk assessment and monitoring, but also on comprehensive evaluation of socioeconomic sustainability. The legislative assessment, therefore, is conducted in two stages: first, the genetic changes on the level of the organism used for the product are considered. Then, the broader societal impact of the product is evaluated and assessed. From the environmental perspective, the direct and the indirect, instantaneous, and accumulating impacts are examined in the evaluation.52 Furthermore, Norway has also expressed the desire to further develop their legislation through public debate. To promote the debate, the Norwegian Biotechnology Advisory Board presented their perspective on a new assessment and approval system in 201853, which would define the required level of assessment of genetically engineered products based on the level of genetic change (figure 2). The level of genetic change could be defined, for example, by determining if the same change could be achieved through traditional breeding methods, or if the change required DNA transfer between species.54 51 Schmidt et al. 2020, 2. 52 Myrh et al. 2020, 641–642. 53 The Norwegian Biotechnology Advisory Board 2018. 54 Eriksson 2019, 572. 35 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 Figure 2.  The Norwegian Biotechnology Advisory Board’s Suggestion for a Regulatory Framework on Gene Technology. Source: The Norwegian Biotechnology Advisory Board 2018. 2.3.3 The Stance of the Court of Justice of the European Union In the EU, genetic modification and editing is mainly regulated with the Gene Technology Legislation of the Union. The most significant regulations on agricultural and food products are directives 2001/18/EC and 1829/2003/EC.55 The field of genetic engineering, especially the utilisation of genome editing techniques in plant breeding and its legal position, has sparked interest during the past few years. The ruling of the Court of Justice of the European Union (CJEU) (case C-528/16) on new mutagenesis techniques on July 25, 201856 in particular raised a lot of discussion. As per the interpretation of the Commission, the ruling of CJEU indicates that the organisms created with the help of genome editing techniques belong under the scope of the GMO directive, and therefore, the corresponding responsibilities of registering, risk assessment, traceability, and monitoring are placed on products derived thereof.57 55 Max Planck Society 2017, 18. 56 Court of Justice of the European Union. PRESS RELEASE No 111/18. Luxembourg, 25 July 2018. [Accessed 18.3.2021] 57 Ewen Callaway. “CRISPR plants now subject to tough GM laws in European Union”. Nature 560, 16 (2018) [Accessed 17.2.2021] Covered by the Gene Technology Act Contribution to societal bene�t, sustainability and ethics required at levels 1-3 Level O (exempted) Temporary and simultaneously non-heritable changes Level 1 Changes that exist or can arise naturally, and can be achieved using conventional breeding methods. Obligation to notify (con�rmation of receipt required) Expedited assessment and approval Standard assessment and approval (current system) Level 2 Other species-speci�c genetic changes Level 3 Genetic changes that crosses species barriers or involve synthetic (arti�cial) DNA-sequences. https://www.mpg.de/13811476/DP-Genome-Editing-EN-Web.pdf%20%20pp18 https://curia.europa.eu/jcms/upload/docs/application/pdf/2018-07/cp180111en.pdf https://curia.europa.eu/jcms/upload/docs/application/pdf/2018-07/cp180111en.pdf https://www.nature.com/articles/d41586-018-05814-6 36 Publications of the Government´s analysis, assessment and research activities 2021:39 According to the CJEU ruling and the interpretation of the Commission, utilising new (post-2001) mutagenesis techniques, as well as genome editing on plants or other living organisms is considered regulatable genetic modification. Therefore, the definition in the GMO directive applies to all organisms that have had their genetic material altered with a mutagenesis technique. Only the ‘traditional’ mutagenesis techniques developed before the GMO Directive came into effect (in 2001) are not considered to belong under the scope of the Gene Technology Regulations of the EU. Chemical and irradiation mutagenesis are examples of such techniques. As a consequence of the ruling, the organisms generated through the new genome editing techniques and genetically modified organisms are not differentiated in legislation: both belong under the scope of GMO legislation, and both include the same responsibilities.58 This association has stirred a lot of controversy especially among scientists, who have highlighted the differences between new genome editing techniques and gene transfer methods. Per the perspective of the majority of scientists, genome editing techniques are more comparable to traditional mutagenesis than to gene transfer techniques.59 According to this perspective, there is no scientific reason or evidence for regulating traditional and new mutagenesis in different ways, because the utilisation of new genome editing techniques produce the same results as the traditional breeding methods, only more quickly and accurately.60 For example, with irradiation random changes are produced in the DNA, and then the plants with the desired traits are chosen from among all others. Whereas genome editing enables generation of specific changes in parts of DNA known to give the desired traits. In fact, the ruling of CJEU has been described thusly: while the ‘dynamite fishing’ of traditional methods is legal, ‘angling’ through new genome editing techniques is prohibited.61 However, several environmental and non-governmental organisations have emphasised that there is still not enough information on the long-term impact of genetic engineering on the environment, people, and animals to reliably evaluate their safety. These actors highlighting the precautionary principle are of the opinion that organisms generated through new genome editing techniques belong strictly under the regulative framework of the GMO directive.62 The suspicions placed on new genome editing techniques are heavily influenced by fears of genetic engineering in general and the view that traditional food production is organic. In general, people are against genome editing techniques for the same reasons GM methods are strongly opposed: both are seen to encompass 58 Wasmer 2019, 4–5. 59 ALLEA 2020, 8. 60 ALLEA 2020, 8. 61 Schulman et al. 2020, 8. 62 Habets et al. 2019, 12–13. 37 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 potential, significant risks to the ecosystem. Furthermore, people are afraid of accidental, so-called off-target mutations.63 Currently, the precautionary principle and securing the traditional European agriculture and food industry are strongly emphasised in the EU regulation. Innovations of new genome editing techniques and other biotechnical methods are seen as a threat towards traditional food production. The current regulation causes products with the same qualities to fall under the scope of different regulations based on the applied techniques. This, in turn, places the products in unequal statuses.64 2.3.4 Potential Consequences of the CJEU Ruling The ruling of CJEU was a massive disappointment to European plant breeders. To illustrate, the European Federation of Academies of Sciences and Humanities ALLEA has encouraged the EU to reconsider the legislation on new genome editing techniques. According to the critique, the legal position of new genome editing techniques requires additional practical clarification and guidance. During Finland’s presidency, the Council of the European Union did, in fact, request the commission to perform a review on the legal position of new genome editing techniques and its implications, which has been completed for delivery at the end of April 2021.65 As of now, the ruling of CJEU is feared to be the death blow to research and development activities on new genome editing techniques, and to the commercialisation of the products created through these techniques in Europe. As a consequence of the ruling, the investments in the field are likely to diminish, since the long and expensive approval process that follows the current legislation makes the commercialisation of the varieties generated through new genome editing techniques extremely difficult. The only actors capable of executing the commercial utilisation of genome editing in the EU are large, multinational enterprises.66 Even large companies that focus on agricultural products, 63 Eric Niiler. “How CRISPR could transform our food supply”. National Geographic, August 10 2018. [Accessed 17.2.2021] 64 Eduskunnan tulevaisuusvaliokunnan julkaisu 2/2018, 11–12. 65 Van der Meer et al. 2021, 3,9–12. The report was published right before the publishing date of this report in the end of January 2021: COMMISSION STAFF WORKING DOCUMENT Study on the status of new genomic techniques under Union law and in light of the Court of Justice ruling in Case C-528/16 https://ec.europa.eu/food/plant/gmo/ modern_biotech/new-genomic-techniques_en. 66 Schulman et al. 2020, 9–10. https://www.nationalgeographic.com/environment/future-of-food/food-technology-gene-editing/ https://www.nationalgeographic.com/environment/future-of-food/food-technology-gene-editing/ https://ec.europa.eu/food/plant/gmo/modern_biotech/new-genomic-techniques_en https://ec.europa.eu/food/plant/gmo/modern_biotech/new-genomic-techniques_en 38 Publications of the Government´s analysis, assessment and research activities 2021:39 such as Bayer and BASF, have threatened to move their genome-editing plant breeding functions outside Europe due to the CJEU ruling.67 In Europe, lagging behind the frontline of global research and development work has caused concern. EU Member states are world-leading actors in research that uses genome editing. However, even now, they are significantly behind China and the United States on commercial application of the research.68 Currently, only eight percent of CRISPR patents are allocated in Europe, while nearly 60 percent of them originate from China, and 26 percent of the patents have been applied from the United States69. In addition, the EU treats agricultural products generated through new genome editing techniques differently from their trade partners all around the world. As of now, marketing of the varieties generated through new genome editing techniques requires extremely extensive risk assessment processes that follow the GMO directive. Based on the producers’ experiences, importing GMO species to the EU costs about 10–15 million euros on average, and it takes several years70. In other words, EU regulations create a significant barrier for marketing varieties generated through new genome editing techniques, since these species are considered GMOs.71 In addition, many fear that implementing the principles of the CJEU ruling will also lead to disruptions in the international trade of agricultural products. To illustrate, the legislation in Argentina, Brazil, and the United States, which import over 30 million tonnes of soy to the EU, does not require their producers to register or track varieties or foodstuffs derived thereof, which are generated through new genome editing techniques, as is the case in the EU. Despite this, the varieties under the scope of the GMO legislation of the EU, such as the above-mentioned genome edited soy, must be approved, and registered before these varieties or products therof can be released to the internal market. However, the issue with varieties generated through new genome editing techniques is that the authorities do not have the necessary technological means to identify them. Indeed, the scientific view is that many changes made by genome editing are impossible to distinguish from ones occurring naturally or by traditional mutagenesis. This means that it is nearly impossible to trace and control the plant breeds generated through genome editing techniques in accordance with the demands from the current GMO legislation of the EU. Therefore, trade with certain countries will either be halted, or varieties generated 67 Reuters. ”Bayer, BASF to pursue plant gene editing elsewhere after EU ruling”. July 27, 2018. [Accessed 17.2.2021] 68 Menz et al. 2020, 14. 69 Schmidt et al. 2020, 1. 70 Schulman et al. 2020, 9. 71 ALLEA 2020, 26–27. https://www.reuters.com/article/us-eu-court-gmo-companies-idUSKBN1KH1NF https://www.reuters.com/article/us-eu-court-gmo-companies-idUSKBN1KH1NF 39 Publications of the Government´s analysis, assessment and research activities 2021:39 Publications of the Government´s analysis, assessment and research activities 2021:39 through new genome editing techniques are definitely going to end up in the EU region as a part of international trade.72 In addition to the economic and legislative challenges, one of the most frequently expressed concerns is the delay on the development of sustainable agriculture and means to combat climate change through plant breeding caused by the current EU ruling on the utilisation of the new genome editing techniques. Fulfilling the objectives of sustainable development by the year 2050 with available water, less fertilisers and smaller acreage requires new and improved varieties. New varieties generated through genome editing are perceived as a crucial method to answer the increasing demands of food production, as well as the global challenges of climate change and population growth.73 There appears to be three potential future options: continuing the current regulatory framework, adapting the current framework, or creating completely new legislation on the topic. At the end of this report, the future of the new genome editing techniques in the EU is discussed in detail in scenarios devised within the framework of this study. 72 Eriksson et al. 2019, 1678–1681; ALLEA 2020, 30. 73 Schulman et al. 2020, 10. 40 Publications of the Government´s analysis, assessment and research activities 2021:39 3 Actors Utilising New Genome Editing Techniques in Finland To gain an overall view, the attempt was made to reach a field of actors who could have insights into the development in the field and its requirements. The actors we came across within this study can be divided into three groups: 1) scientific communities and research institutes; 2) government, organisations, and foundations; 3) companies. 3.1 Scientific Communities and Research Institutes The utilisation of new genome editing techniques both in Finland and in Europe relies heavily on science and research. Therefore, there are many institutes conducting research or developing new applications based on genome editing techniques in Finland as well. During this study, at least the following 15 domestic and international organisations were identified. They are already operating and in central positions in the research and development of genome editing techniques: y Biomedicum Stem Cell Center (BSCC) y Cost Action: Genome Editing in Plants - a Technology with Transformative Potential (PlantEd) CA18111, University of Lund, Sweden) y European Plant Science Organisation (EPSO) y European Technology Platform – Plants for the Future y University of Helsinki y University of Eastern Finland y KCT Kuopio Center for Gene and Cell Therapy y National Resources Institute Finland (LUKE) y Institute for Molecular Medicine Finland (FIMM) y Finnish Environmental Institute (Syke) y VTT Technical Research Centre of Finland Ltd (VTT) y Finnish Institute for Health and Welfare (THL) y University of Turku y Åbo Akademi University