Shotguns vs Lasers: Identifying barriers and facilitators to scaling-up plant molecular farming for high-value health products

Abstract

Plant molecular farming (PMF) is a convenient and cost-effective way to produce high-value recombinant proteins that can be used in the production of a range of health products, from pharmaceutical therapeutics to cosmetic products. New plant breeding techniques (NPBTs) provide a means to enhance PMF systems more quickly and with greater precision than ever before. However, the feasibility, regulatory standing and social acceptability of both PMF and NPBTs are in question. This paper explores the perceptions of key stakeholders on two European Union (EU) Horizon 2020 programmes-Pharma-Factory and Newcotianatowards the barriers and facilitators of PMF and NPBTs in Europe. One-on-one qualitative interviews were undertaken with N = 20 individuals involved in one or both of the two projects at 16 institutions in seven countries (Belgium, France, Germany, Italy, Israel, Spain and the UK). The findings indicate that the current EU regulatory environment and the perception of the public towards biotechnology are seen as the main barriers to scaling-up PMF and NPBTs. Competition from existing systems and the lack of plant-specific regulations likewise present challenges for PMF developing beyond its current niche. However, respondents felt that the communication of the benefits and purpose of NPBT PMF could provide a platform for improving the social acceptance of genetic modification. The importance of the media in this process was highlighted. This article also uses the multi-level perspective to explore the ways in which NPBTs are being legitimated by interested parties and the systemic factors that have shaped and are continuing to shape the development of PMF in Europe. PLOS ONEPLOS ONE | https://doi.org/10.1371/journal.pone.The use of plants as platforms for the expression of recombinant proteins was first demonstrated in the late 1980s and early 1990s -primarily with the tobacco plant [23][24][25]. It would take over a decade for the first commercial product to be launched [8], but since that time a PLOS ONEBarriers and facilitators to scaling-up plant molecular farming PLOS ONE | https://doi.org/10.Barriers and facilitators to scaling-up plant molecular farming PLOS ONE | https://doi.org/10.

New Hope for a “Cursed” Crop? Understanding Stakeholder Attitudes to Plant Molecular Farming With Modified Tobacco in Europe

“…Following previous research that explored the perceptions of Newcotiana consortium researchers and businesses toward the barriers and facilitators of PMF and NPBTs (Menary et al, 2020), relevant key stakeholders in the production and distribution of tobacco were hypothesized to be existing tobacco farmers, their advisors and producer associations, as well as policy makers and researchers familiar with tobacco production. Onward supply chain stakeholders such as pharmaceutical companies and regulators are being queried in other Newcotiana work packages.…”

“…The second risk is that the structure of the industry, with political and economic power concentrated in large, influential businesses, could make POs hesitant to support the development of new technologies seen to challenge the status quo. PMF already faces some challenges due to the technological "lock-in" of existing protein expression systems (e.g., prior legislation that favors cell culture technology and not plants and sunk investments in those systems) (Menary et al, 2020). Those companies explicitly opposed to genetic modification at this time -Imperial Brands (Our Views -Imperial Brands, 2019), British American Tobacco (British American Tobacco -Leaf research, 2019), and Altria Group (Altria Group, 2016) -may therefore perceive PMF as a contaminant threat to their non-GM crops, if not also a threat to the availability of growers themselves (Nevitt et al, 2003) 4 .…”

“…The multi-level perspective describes a number of levels -niches (where radical innovation emerges), the socio-technical regime (current ways of doing things that are stabilized through behavior, vested interests and existing regulations) and the socio-technical landscape (the slowchanging exogenous environment) -that can be used to explain the gradual development of PMF in Europe. Menary et al (2020) describe how the existing socio-technical regime has been one of several factors constraining PMF; existing regulations do not reflect the advantages offered by plants and significant investment in cell culture alternatives by pharmaceutical companies deters investment in plant-made alternatives.…”

“…Open-field PMF presents a number of additional challenges in this respect, such as the uniformity of plants grown under changeable cultivation conditions and the risk of contamination, both in terms of the molecules themselves and the unwanted spread of GM plants (Mascia and Flavell, 2004;Breyer et al, 2009). Whether openfield PMF for biopharmaceuticals can ever meet the strict criteria laid out in good manufacturing practice guidelines has been questioned by leading PMF scientists (Menary et al, 2020). However, the development of enriched, open-field Newcotiana N. tabacum feedstock lines that are intragenic (i.e., containing novel combinations of native genetics but no transgenes) and destined for biorefinery use is intended to be a "proving ground" for the efficacy of NPBTs in Europe and a means to demonstrate the reliability of PMF platforms.…”

Plant Molecular Farming: A Viable Platform for Recombinant Biopharmaceutical Production

“…The expression methods used for the recombinant protein production in plants can be either stable or transient expression. PMF relies on following approaches for the expression of vaccine candidates, i.e., stable nuclear transformation, stable chloroplast transformation, or transient expression, by using plant viral vectors and stable transformation of hydroponically grown plants in which recombinant proteins are recovered from the medium [119] (Figure 1). Stable nuclear transformation is the traditional strategy of genetic manipulation in plants for recombinant protein production.…”