Perspectives on Genetically Engineered Microorganisms and Their Regulation in the United States.

Genetically engineered microorganisms (GEMs) represent a new paradigm in our ability to address the needs of a growing, changing world. GEMs are being used in agriculture, food production and additives, manufacturing, commodity and noncommodity products, environmental remediation, etc., with even more applications in the pipeline. Along with modern advances in genome-manipulating technologies, new manufacturing processes, markets, and attitudes are driving a boom in more products that contain or are derived from GEMs. Consequentially, researchers and developers are poised to interact with biotechnology regulatory policies that have been in effect for decades, but which are out of pace with rapidly changing scientific advances and knowledge. In the United States, biotechnology is regulated by multiple agencies with overlapping responsibilities. This poses a challenge for both developers and regulators to simultaneously allow new innovation and products into the market while also ensuring their safety and efficacy for the public and environment. This article attempts to highlight the various factors that interact between regulatory policy and development of GEMs in the United States, with perspectives from both regulators and developers. We present insights from a 2022 workshop hosted at the University of California, Berkeley that convened regulators from U.S. regulatory agencies and industry developers of various GEMs and GEM-derived products. We highlight several new biotechnologies and applications that are driving innovation in this space, and how regulatory agencies evaluate and assess these products according to current policies. Additionally, we describe recent updates to regulations that incorporate new technology and knowledge and how they can adapt further to effectively continue regulating for the future.

Revisions to USDA biotechnology regulations: The SECURE rule.

In keeping with the directive in Executive Order 13874 (Modernizing the Regulatory Framework for Agricultural Biotechnology Products) to adopt regulatory approaches that are proportionate to risk and avoid arbitrary distinctions across like products, the US Department of Agriculture (USDA) revised its biotechnology regulations by promulgating the Sustainable, Ecological, Consistent, Uniform, Responsible, and Efficient (SECURE) rule. Specifically, the SECURE rule 1) establishes exemptions for plants modified by genetic engineering where the modification could otherwise have been made through conventional breeding, 2) uses risk posed by the introduced trait to determine whether an organism is regulated, rather than relying on whether the organism was developed using a plant pest, and 3) provides a mechanism for a rapid initial review to efficiently distinguish plants developed using genetic engineering that do not pose plausible pathways to increased plant pest risk from those that do. As a result of the focused oversight on potentially riskier crops developed using genetic engineering, USDA is expected to improve the efficiency and effectiveness of its oversight program. The reduced regulatory burden is expected to promote innovation by expanding the number and diversity of developers to include smaller businesses and academics and to increase the number and variety of traits being developed through biotechnology.

Genetic Engineering of Livestock: The Opportunity Cost of Regulatory Delay.

Genetically engineered (GE) livestock were first reported in 1985, and yet only a single GE food animal, the fast-growing AquAdvantage salmon, has been commercialized. There are myriad interconnected reasons for the slow progress in this once-promising field, including technical issues, the structure of livestock industries, lack of public research funding and investment, regulatory obstacles, and concern about public opinion. This review focuses on GE livestock that have been produced and documents the difficulties that researchers and developers have encountered en route. Additionally, the costs associated with delayed commercialization of GE livestock were modeled using three case studies: GE mastitis-resistant dairy cattle, genome-edited porcine reproductive and respiratory syndrome virus-resistant pigs, and the AquAdvantage salmon. Delays of 5 or 10 years in the commercialization of GE livestock beyond the normative 10-year GE product evaluation period were associated with billions of dollars in opportunity costs and reduced global food security.

Controlling CRISPR Through Law: Legal Regimes as Precautionary Principles.

Since its advent in 2012, CRISPR has spawned a cottage industry of bioethics literature. One principal criticism of the technology is its virtually instant widespread adoption prior to deliberative bodies conducting a meaningful ethical review of its harms and benefits-a violation, to some, of bioethics' "precautionary principle." This view poorly considers, however, the role that the law can play-and does, in fact, play-in policing the introduction of ethically problematic uses of the technology. This Perspective recounts these legal regimes, including regulatory agencies and premarket approval, tort law and deterrence, patents and ethical licenses, funding agencies and review boards, as well as local politics. Identifying these legal regimes and connecting them to the precautionary principle should be instructive for bioethicists and policy makers who wish to conduct ethical reviews of new applications of CRISPR prior to their introduction.

Democratic Governance of Human Germline Genome Editing.

An international regulatory commission convened by scientific academies is a premature and problematic approach to governing human germline genome editing. Given the complex, international landscape of genome editing and significant cross-national differences among regulatory cultures, deferring to a single commission to set the agenda for global governance raises troublesome questions of framing and representation. Rather, democratic governance on a global level demands a new mechanism for active, sustained reflection by scientists on their own practices, conducted in partnership with scholars from other disciplines, as well as public representatives from varied social, political, and religious backgrounds. To be legitimate, ideas of the right form of governance in this emerging and highly consequential area of research need to be opened up to a wider diversity of views and voices.

Heritable Genome Editing and the Downsides of a Global Moratorium.

In 2018, Dr. He Jiankui reported that he had edited human embryos and transferred them to a woman, causing her to give birth to twin girls with modified genomes. An international group of scientists and ethicists responded by proposing a global moratorium on heritable genome editing (HGE). In this article, I oppose this proposal on several grounds. A global moratorium might encourage participating nations to ban HGE or postpone access to it indefinitely. It might also deter or delay basic research that could lead to safe and effective HGE. Lastly, a global moratorium might induce participating nations to adopt or maintain laws and regulations that stigmatize children born with modified genomes. As an alternative, I argue that nations should regulate HGE for safety and efficacy only and without distinguishing between therapeutic and enhancing modifications.

Canadian regulatory aspects of gene editing technologies.

The development of gene editing techniques, capable of producing plants and animals with new and improved traits, is revolutionizing the world of plant and animal breeding and rapidly advancing to commercial reality. However, from a regulatory standpoint the Government of Canada views gene editing as another tool that will join current methods used to develop desirable traits in plants and animals. This is because Canada focusses on the potential risk resulting from the novelty of the trait, or plant or animal product entering the Canadian environment or market place, rather than the process or method by which it was created. The Canadian Food Inspection Agency is responsible for the regulation of the environmental release of plants with novel traits, and novel livestock feeds, while Health Canada is responsible for the regulation of novel foods. Environment and Climate Change Canada, in partnership with Health Canada, regulates modified animals for entry into the environment. In all cases, these novel products may be the result of conventional breeding, mutagenesis, recombinant DNA techniques or other methods of plant or animal breeding such as gene editing. This novelty approach allows the Canadian regulatory system to efficiently adjust to any new developments in the science of plant and animal breeding and allows for risk-appropriate regulatory decisions. This approach encourages innovation while maintaining science-based regulatory expertise. Canadian regulators work cooperatively with proponents to determine if their gene editing-derived product meets the definition of a novel product, and whether it would be subject to a pre-market assessment. Therefore, Canada's existing regulatory system is well positioned to accommodate any new innovations or technologies in plant or animal breeding, including gene editing.

Report on the SCRA Nuts and Bolts Workshop II: case studies of citrus greening, Ultra-low Gossypol Cotton, and blight tolerant, low-acrylamide potato.

To be commercialized and grown in the US, genetically engineered (GE) crops typically go through an extensive food, feed, and environmental safety assessment process which, in certain instances, requires complex consultations with three different US regulatory agencies. Many small market, niche, and specialty crops have been genetically engineered using the modern tools of recombinant DNA but few have been commercialized due to real or perceived regulatory constraints. This workshop discussed the practical aspects of developing dossiers on GE specialty, niche, or small-market crops/products for submission to US regulatory agencies. This workshop focused on actual case studies, and provided an opportunity for public or private sector scientists and crop developers to spend time with regulatory officials to learn the specifics of compiling a dossier for regulatory approval. The objective of the workshop was to explain and demystify data requirements and regulatory dossier compilation by small companies, academics, and other developers.

Are current EU policies on GMOs justified?

The European Court of Justice's recent ruling that the new techniques for crop development are to be considered as genetically modified organisms under the European Union's regulations exacerbates the need for a critical evaluation of those regulations. The paper analyzes the regulation from the perspective of moral and political philosophy. It considers whether influential arguments for restrictions of genetically modified organisms provide cogent justifications for the policies that are in place, in particular a pre-release authorization requirement, mandatory labelling, and de facto bans (in the form of withholding or opting out of authorizations). It is argued that arguments pertaining to risk can justify some form of pre-release authorization scheme, although not necessarily the current one, but that neither de facto bans nor mandatory labelling can be justified by reference to common arguments concerning naturalness, agricultural policy (in particular the promotion of organic farming), socio-economic effects, or consumers' right to choose.

In vitro gametogenesis and reproductive cloning: Can we allow one while banning the other?

In vitro gametogenesis (IVG) is believed to be the next big breakthrough in reproductive medicine. The prima facie acceptance of this possible future technology is notable when compared to the general prohibition on human reproductive cloning. After all, if safety is the main reason for not allowing reproductive cloning, one might expect a similar conclusion for the reproductive application of IVG, since both technologies hold considerable and comparable risks. However, safety concerns may be overcome, and are presumably not the sole reason why cloning is being condemned. We therefore assess the non-safety arguments against reproductive cloning, yet most of these can also be held against IVG. The few arguments that cannot be used against IVG are defective. We conclude from this that it will be hard to defend a ban on reproductive cloning while accepting the reproductive use of IVG.

Will CRISPR Germline Engineering Close the Door to an Open Future?

The bioethical principle of autonomy is problematic regarding the future of the embryo who lacks the ability to self-advocate but will develop this defining human capacity in time. Recent experiments explore the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 for germline engineering in the embryo, which alters future generations. The embryo's inability to express an autonomous decision is an obvious bioethical challenge of germline engineering. The philosopher Joel Feinberg acknowledged that autonomy is developing in children. He advocated that to reserve this future autonomy, parents should be guided to make ethical decisions that provide children with open futures. Here, Feinberg's 1980 open future theory is extended to the human embryo in the context of CRISPR germline engineering. Although the embryo does not possess the autonomous decision-making capacity at the time of germline engineering, the parental decision to permanently change the unique genetic fabric of the embryo and subsequent generations disregards future autonomy. Therefore, germline engineering in many instances is objectionable considering Feinberg's open future theory.

Germline Interventions in Humans - Challenges for Law and Ethics / Intervenciones en línea germinal en seres humanos: desafíos para el Derecho y la Ética

The discovery of new methods of genetic engineering has revolutionized genetic research and opens up new ways of gene therapies. The molecular tool known as CRISPR/Cas9 in particular allows researchers to alter the human genome with unprecedented precision. This new method is referred to as "genome editing," since the procedure is reminiscent of the correction of a text: "false" letters of the DNA can simply be replaced. Due to the precision and the simple application of this method, the focus is now on a field of application that was previously considered an absolute taboo: germline interventions. Any interference with the human germline causes the corresponding genetic changes to be passed on from generation to generation. The issue is highly controversial, and the arguments for and against interventions are diverse. Their proponents argue that future descendants will thus be freed from serious genetic diseases. Opponents, on the other hand, believe that this path must always remain off limits in order to prevent the conception of "designer children." It is clear that such interventions should not yet take place at the moment: more research is needed in order to allow for a more precise risk-benefit-assessment. In fact, the research community seemed to agree that the techniques are not yet sufficiently developed. However, the rumoured birth of two genetically modified children in China at the end of November 2018 shows that such a consensus either does not exist or, at least, that we cannot trust rely on all researchers acting in accordance with the scientific consensus. This news therefore highlights yet again how urgently we must discuss the issue: it is high time, also given the possibility of rapid improvements in the techniques' safety, to deliberate on the justifiability of germline interventions and to set clear limits. This article is intended to contribute to this debate and to sketch the main arguments

The discovery of new methods of genetic engineering has revolutionized genetic research and opens up new ways of gene therapies. The molecular tool known as CRISPR/Cas9 in particular allows researchers to alter the human genome with unprecedented precision. This new method is referred to as "genome editing," since the procedure is reminiscent of the correction of a text: "false" letters of the DNA can simply be replaced. Due to the precision and the simple application of this method, the focus is now on a field of application that was previously considered an absolute taboo: germline interventions. Any interference with the human germline causes the corresponding genetic changes to be passed on from generation to generation. The issue is highly controversial, and the arguments for and against interventions are diverse. Their proponents argue that future descendants will thus be freed from serious genetic diseases. Opponents, on the other hand, believe that this path must always remain off limits in order to prevent the conception of "designer children." It is clear that such interventions should not yet take place at the moment: more research is needed in order to allow for a more precise risk-benefit-assessment. In fact, the research community seemed to agree that the techniques are not yet sufficiently developed. However, the rumoured birth of two genetically modified children in China at the end of November 2018 shows that such a consensus either does not exist or, at least, that we cannot trust rely on all researchers acting in accordance with the scientific consensus. This news therefore highlights yet again how urgently we must discuss the issue: it is high time, also given the possibility of rapid improvements in the techniques' safety, to deliberate on the justifiability of germline interventions and to set clear limits. This article is intended to contribute to this debate and to sketch the main arguments

La eliminación de taras o enfermedades graves como elemento del tipo del delito de manipulación genética / The elimination of serious defects or diseases as a substantial element of the genetic manipulation offence

La introducción de los delitos relativos a la manipulación genética en el Código penal de 1995 fue celebrada como uno de los muchos aciertos que la política criminal contemporánea ha tenido y como una necesaria y urgente adaptación del Derecho penal a los avances científicos en la materia. Desde su creación el tipo penal recogido en el artículo 159 del Código penal ha recibido una necesaria labor interpretativa que la doctrina penal especializada ha llevado a cabo sobre su ubicación sistemática, su estructura general, los intereses protegidos en él, la conducta típica y la técnica de tipificación utilizada por el legislador al diseñar su morfología y elementos. En este trabajo se lleva a cabo el análisis de un segmento del tipo del artículo 159.1 del Código penal, compuesto todo él por elementos de difícil interpretación, centrándome en los conceptos de taras y de enfermedades graves, que son los utilizados por el legislador para complementar con un elemento intencional la estructura del tipo objetivo del delito. Debemos analizar secuencialmente su naturaleza y textura, su función en el contexto del tipo, su relación con el resto de elementos de la conducta típica y el proceso de determinación de su contenido. Ello nos aboca frontalmente con dilucidar si se trata de causas de justificación o elementos del tipo, y de ahí se derivará qué función tienen respecto al dolo del autor y la tipología del error sobre ellos

The introduction of crimes related to genetic manipulation in the 1995 Penal Code was celebrated as one of the many successes that contemporary criminal policy has had and as a necessary and urgent adaptation of criminal law to scientific advances in the matter. Since its creation, the criminal prohibition in the article 159 of the Criminal Code has received a necessary interpretative work that the specialized criminal science has carried out on its location, its general structure, the protected interests, the punished behavior and the technics on engineering used by the legislator when designing its morphology and elements. In this work is carried out the analysis of a part of the article 159.1 of the Penal Code, composed all of it by elements of difficult interpretation, focusing on the concepts of "defects" and "serious diseases", which are those used by the legislator to complement with an intentional element the structure of the crime. On these elements we must analyze sequentially its nature and texture, its function in the context of the criminal offence of which they are a part, its relationship with the rest of the elements and the process of filling its meaning. This leads us to determine whether these are causes of justification or elements of the criminal offence, and from there we will derive what role they have regarding the author's intent and the typology of the error cases on these elements

Bioderecho, genotipo y derecho penal colombiano. Acerca de los problemas de tutelar penalmente un bien jurídicode naturaleza colectiva / Biolaw, genotype and colombian criminal law. About the problems of protecting a legal interest of collective nature

El artículo analiza críticamente, desde la perspectiva del bioderecho, la regulación penal de la manipulación genética en Colombia, evidenciando alguna de sus deficiencias más importantes, especialmente aquella de tutelar un bien jurídico de naturaleza colectiva. Luego, se elaboran y justifican algunas críticas a la construcción del tipo penal de manipulación genética para, finalmente, sustentar una propuesta de optimización de dicha regulación. Se concluirá que i) la estructura de la actual regulación penal de la manipulación genética en Colombia carece de exhaustividad y es imprecisa en, prácticamente, todos los puntos analizados en este trabajo, y que ii) el bioderecho representa un modelo jurídico capaz de otorgar más seguridad a la regulación penal de la manipulación genética en Colombia y otros ordenamientos legales del mundo

In this paper I critically analyze, from biolaw's point of view, the criminal regulation of genetic manipulation in Colombia by evidencing some of its most important deficiencies, especially in relation to protecting a legal interest of a collective nature. Then, some criticisms are elaborated and justified regarding the construction of the criminal type of genetic manipulation to finally offer and support a proposal of optimization for that regulation. It will be concluded that i) the structure of the current criminal regulation of genetic manipulation in Colombia lacks exhaustiveness and is imprecise in practically all the points analyzed in this work, and that ii) biolaw represents a legal model capable of granting more security and certainty to the criminal regulation of genetic manipulation in Colombia, as well as to other legal systems in the world

Due Diligence, Precautionary Principle and the so-called GMO Directive: a brief commentary on the ECJ's judgement on the case "Confédération paysanne and Others v. Premier Ministre and Ministre de l'Agriculture, de l'Agroalimentaire et de la Forêt" / Diligencia Debida, Principio de Precaución y la Directiva de OMG: un breve comentario sobre la sentencia del TJUE en el caso "Confédération paysanne and Others v. Premier Ministre and Ministre de l'Agriculture, de l'Agroalimentaire et de la Forêt"

Recently, on the 25th July 2018, the ECJ decided that "organisms obtained by mutagenesis are GMOs and are, in principle, subject to the obligations laid down by the GMO Directive". Considering the huge impact of the Court's decision, I decided to write a brief commentary on the arguments invoked by the Luxembourg judges, analysing specifically the scope, content and role of the precautionary principle in the context of a World Risk Society (Beck). Also, I criticize the activist attitude of the Court, which I consider may have gone too far in the interpretation of Directive 2001/18/EC. Finding balance between the "guaranteeing" role of bioethics and Law and the need for a free and highly encouraged scientific activity is, undoubtedly, one of the main challenges we must face nowadays. This judgement is, in that context, a good example of the difficulties one may encounter on the way

Recientemente, el 25 de julio de 2018, el Tribunal de Justicia de la Unión Europea decidió que "los organismos obtenidos por mutagénesis son OMG y, en principio, están sujetos a las obligaciones establecidas por la Directiva de OMG". Teniendo en cuenta el enorme impacto de la decisión de la Corte, resulta oportuno el comentario jurisprudencial que, a continuación, se incluye, sobre los argumentos invocados por los jueces de Luxemburgo, especialmente analizando el alcance, contenido y el papel del principio de precaución en el contexto de la Sociedad Mundial del Riesgo (Beck). Además, el trabajo incluye una crítica a la actitud activista de la Corte, que, en opinión del autor, ha ido demasiado lejos en la interpretación de la Directiva 2001/18/EC. Encontrar el equilibrio entre el papel "garantista" de la Bioética y del Derecho y la necesidad de una actividad científica libre y altamente alentada es, sin duda, uno de los principales desafíos a los que nos enfrentamos en la actualidad. Esta decisión jurisprudencial es, en ese contexto, un buen ejemplo de las dificultades que uno se podrá encontrar en el camino

Mexico and mitochondrial replacement techniques: what a mess.

Background: The first live birth following the use of a new reproductive technique, maternal spindle transfer (MST), which is a mitochondrial replacement technique (MRT), was accomplished by dividing the execution of the MST procedure between two countries, the USA and Mexico. This was done in order to avoid US legal restrictions on this technique. Sources of data: Academic articles, news articles, documents obtained through freedom of information requests, laws, regulations and national reports. Areas of agreement: MRTs are new reproductive techniques that present novel ethical and legal challenges, since genetic material from three people is employed to create a child. Areas of controversy: Could the first MST procedure that culminated in a live birth negatively impact reproductive medicine in Mexico? Growing points: The USA and Mexico need specific and clear legislation on MRTs, in order for such techniques not to be governed by prior existing legislation on assisted reproduction that is inadequate for dealing with the new challenges that these techniques present. Areas timely for developing research: There is a pressing need for work to be done on the international governance of new reproductive techniques.