Open Agriculture. 2017; 2: 160–165 Review Article Open Access D. Caballero-Hernandez*, C. Rodríguez-Padilla, S. Lozano-Muñiz Bioethics for Biotechnologists: From Dolly to CRISPR DOI 10.1515/opag-2017-0016 Received January 5, 2017; accepted February 22, 2017 1 Introduction Abstract: Bioethics, as a discipline, has developed mainly, but Bioethics has evolved from a discipline mostly perceived as not exclusively, around themes of moral importance for the being focused on moral issues ranging from medical practice medical practice, such as abortion and euthanasia, a never to a wider endeavor where concerns regarding the nature ending discussion that has been shaped by social mores and of human identity, animal welfare and the environment influenced by scientific and technological advance. However, are becoming increasingly important, if not central. This is in the past 20 years an important shift has been taking place, the result of the unrelenting pace at which the life sciences one where bioethical issues and their discussion are starting and biotechnology are advancing, defying old paradigms to being driven by the so-called emerging biotechnologies, and creating new ones. The past 20 years have witnessed 3 from cloning to genome sequencing and editing. If Bioethics milestones in the life sciences; the birth of the first cloned is concerned with human beings, and their interaction with mammal, Dolly (Callaway 2016), the completion of the other living beings and the environment, it makes sense for Human Genome Project (Venter et al. 2001) and the discovery Biotechnology, by definition the use of living systems or and harnessing of CRISPR, a game changer in the field of organisms to develop products, to become an important, genome editing (Mariscal and Petropanagos 2016). if not the most important, source of bioethical conflicts in The main goal of biotechnology is and has always been modern era and for future society. As Biotechnology keeps to improve people’s lives; this is in line with ethical goals expanding and becomes entangled in everyday life, so and is in itself an ethical vision. Animal domestication, does the need for ethical competent biotechnologists, with agriculture and fermentation, all contributed to a competencies built not only on ethical principles but also on better quality of life with the consequent expansion of a realistic grasp of the impact these technologies could have human population through the planet. More recently, on human society and the world we inhabit. technological and medical advances such as nitrogen fixation, vaccines and antibiotics have contributed to a Keywords: Biotechnology, genome editing, animal longer life expectancy and population explosion arising cloning, ethics, fairness, biothreats, biosafety, biosecurity important issues, perhaps the most important the allocation of resources in a world edging close to ecological exhaustion. It is to be expected that many of the emerging biotechnologies of today will become an established part of daily life in the future. But will these changes be positive *Corresponding author: D. Caballero-Hernandez, Laboratorio for society? Have the risks and benefits been analysed? de Inmunología y Virología, Facultad de Ciencias Biológicas, All these changes often occur without consultation with Universidad Autónoma de Nuevo León (UANL), Mexico, E-mail: the general population, and sometimes without ethical [email protected] reflection on the part of the scientists and technologists C. Rodríguez-Padilla, Laboratorio de Inmunología y Virología, Facult- ad de Ciencias Biológicas, Universidad Autónoma de Nuevo León involved (O’Mathúna 2007). (UANL), Mexico S. Lozano-Muñiz, Universidad del Papaloapan, Mexico S. Lozano-Muñiz,Sociedad Mexicana de Biotecnología y Bioinge- 2 Biotechnology: the road to niería, Delegación Oaxaca, Mexico S. Lozano-Muñiz,International Foundation for Biotechnology Re- genetic engineering search & Early Stimulation in the Culture of Health, Nutrition, Sport, Art, Science, Technology & Society.A.C.- International Biotechnology The history of biotechnology can be roughly divided Foundation, Mexico into three categories: Ancient Biotechnology, Classical © 2017 D. Caballero-Hernandez et al., published by De Gruyter Open. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivsBrought 3.0 License. to you by | Universidad Autónoma de Nuevo León Authenticated Download Date | 3/13/19 9:20 PM Bioethics for Biotechnologists: From Dolly to CRISPR 161 Biotechnology and Modern Biotechnology. While ancient biotechnology can be described as a series of developments, such as the domestication of plants and animals and sometimes accidental discoveries, like bread, cheese and wine, Classical Biotechnology lingers as a transitional period were the fundamental tenets of genetics and molecular biology were established. Modern Biotechnology officially started from the second half of the 20th century with the development of tools for the manipulation of nucleic acids, cloning and recombinant DNA technology (rDNA), critical for the development of genetic engineering (Verma et al. 2011). It is interesting to note that Bioethics and Modern Biotechnology were born around the same time and although there is discrepancy regarding the origin of the word “bioethics” there is agreement it was coined between 1970 and 1972 (Pellegrino 1999; Martensen 2001). In 1972, Paul Berg created the first recombinant DNA molecule; the next year Boyer and Figure 1: Genetic engineering (GE) involves the manipulation and/ Cohen created the first genetically modified organism, or modification of the genome of living beings, for 3 decades recom- these events marked the birth of genetic engineering as a binant DNA remained the main tool of GE but recently, engineered force for technological advance (Giassetti 2013). endonucleases (GEEN) such as ZFNs and TALENs have proved to For almost three decades, up to 2012, recombinant be a more precise and efficient tool, the discovery of the CRISPR/ DNA technology had proved to be a solid tool for genetic Cas9 system took this one step further, revolutionizing GE. To differentiate from recombinant DNA technology, the modification of engineering. Despite limitations: time-consuming, lacks genomes using endonucleases is known as genome editing. Despite precision, low efficiency and high costs, it remained for not involving modification of the genome, cloning is considered by many years the backbone of genetic engineering, along many a type of GE with DNA sequencing and the Polymerase Chain Reaction (PCR). Given the limitations of the technique, rDNA was CRISPR stands for Clustered regularly interspaced better suited for single cell organisms and bacteria, and short palindromic repeats, short snippets of viral DNA since the 1970’s a vast array of medical and industrial inserted into a bacterial genome, acting as spacers applications have been developed: human insulin and and working as a template to synthesize a type of growth hormone-producing recombinant bacteria being interference RNA, able to recognize specific points among the most important. Recombinant DNA technology in the genome of an infecting virus to mark sites to also became a tool for research in laboratories around the be cut by nucleases (Gaj et al. 2013). Cas9 is the most world. recognized of these nucleases, but others, such as Genome editing as a new approach in genetic Cpf1, have been recently discovered, expanding the engineering started to develop recently and aim to toolbox of genetic engineering. If recombinant DNA manipulate the genome by adding, subtracting or technology was a step forward, CRISPR could be replacing genes inducing site-specific breaks in the DNA described as a quantum leap for genetic engineering using nucleases, enzymes able to cut DNA, and taking and for the emerging biotechnologies of transgenic advantage of the natural DNA repair system to close the plant and animal development, synthetic biology, gap. Zinc-finger nucleases (ZFN) were discovered in 2002, nanotechnology, xenotransplantation, gene therapy followed by transcription activator-like effector nucleases and population control through gene drives. These (TALENs), which represented a significant advance in so-called emerging biotechnologies represent the next the ability to control the manipulation of DNA. However, stage in the development of Biotechnology one that despite the improvement in precision, both ZFN and now aspires not only to use living beings to develop TALENs still needed significant expertise and resources, products, but also to tailor organisms through genome limiting widespread use. This all changed with the editing or synthetic biology approaches, to obtain discovery of CRISPR/Cas9, a natural system of bacterial new products for human use and consumption. These defense against bacteriophages, reinvented as a precision technologies make the ethical training of students and tool for the editing of the genome (Maxmen 2015; Au 2015) Brought to you by | Universidad Autónoma de Nuevo León Authenticated Download Date | 3/13/19 9:20 PM 162 D. Caballero-Hernandez, et al. professionals of biotechnology in general even more 4 Ethical reflection in urgent (Rasmussen and Ebbesen 2014). Biotechnology The four ethical principles are useful for the discussion of the many challenges brought by emerging biotechnologies, particularly DNA-based technologies. The first ethical principle is beneficence, a moral imperative to contribute to other people’s