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The progress in molecular biology, from the discovery of DNA structure in the 1950s through understanding how it functions to encode proteins in the 1960s and the introduction of genetic engineering in the 1970s, created the possibility of moving genes from one organism to another. This process, called transgenesis, results in the formation of organisms which did not exist in nature but were made for a speciﬁc purpose, which can be research, therapy, testing a crop plant with new possibilities, etc. A lot of the discussions concerning transgenesis took place in the mid and late 1970s, when the main element was the fear of the consequences of creating new forms of life and to some extent asking whether this was an admissible thing to do. Currently, this has been replaced by several kinds of discussions, which are also mentioned in other entries in this encyclopedia, such as the rights of animals, fear of genetically modiﬁed organisms, and others. The history and consequences of transgenesis for science and society are discussed in this research paper.
In the last 40 years, few things in science have aroused so many discussions and controversies as the introduction of genetic engineering in the early 1970s and the transgenic organisms which were constructed using this technique. The consequences of this change have been tremendous, affecting biomedical sciences and accelerating their development and on the other hand raising questions pertaining to what man can and what he should not do with the genetic material of living organisms.
History And Development
It is currently very difﬁcult to imagine our world without a hepatitis B vaccine or a human insulin in practically every pharmacy. These therapeutic products are made by microorganisms containing genes which their natural relatives do not have, as they were introduced by man for the purpose of obtaining cells which produce a protein which can be useful for treatment of diseases or other purposes.
The road leading to these achievements is to a large extent that of the development of genetics and molecular biology, but a good starting point is the discovery of the structure of DNA in 1953. This led to the understanding of what our genetic material is and how it replicates and sometime later, in the 1960s, to understanding the genetic code –that DNA is made up of genes, which (generally) encode proteins. At that time, some progress was also made in understanding how genes are regulated, but this knowledge was limited to genes in bacteria. There were no tools to look at the structure or regulation of the genes of higher organisms, and implicitly it was assumed that bacteria and other, more complicated forms of life had very similar ways of regulating genes and their expression.
In the early 1970s, certain enzymes (called restriction enzymes) were found to cut DNA in a reproducible fashion, and another enzyme (ligase) was shown to join fragments of DNA. Special carriers called vectors were made into which DNA fragments could be inserted, and these constructs could multiply after introduction into a host cell, and thus genetic engineering was born. The very ﬁrst transgenic organism was a laboratory strain of the bacterium Escherichia coli carrying a fragment of DNA from the toad Xenopus (Berg and Mertz 2010). Progress of genetic engineering was so rapid, and the ﬁeld itself offered such unexpected possibilities that the scientists became worried about what these new methods could lead to. Already in 1973, the US Academy of Sciences was asked to analyze the danger of the new technology, and in 1974 the famous “moratorium letter” appeared in the journal Science. It was signed among others by James Watson (already a Nobel Prize winner in 1963 for discovering the structure of DNA) and Paul Berg (Berg et al. 1974). Berg, in whose laboratory many of the ﬁrst experiments of genetic engineering took place, would go on to win the Nobel Prize in 1980 for “his fundamental studies of the biochemistry of nucleic acids with particular regard to recombinant DNA” (Nobelprize.org). Recombinant DNA was the name used for the DNA which was the effect of genetic engineering as it combined non-naturally occurring DNA molecules. The moratorium letter asked that investigations on recombinant DNA be stopped until the potential dangers of this work could be evaluated. The letter could be said to constitute an expression of increasingly felt ethical concerns about the uncertainty of the genetic manipulations.
In 1975, in Asilomar the famous “Pandora’s box congress” took place with 140 participants discussing the potential dangers of genetic engineering. Four categories of risk associated with genetic engineering were established (from “minimal” to “high”) with appropriate requirements for laboratory procedures and containment facilities. These four categories still persist, at least in Europe, in the classiﬁcation of work with genetically modiﬁed organisms (GMOs). As work was resumed, the fears of Frankenstein-like cancercausing bacteria were slowly allayed, and the stringent rules of containment were gradually relaxed. Initially, the only transgenic organisms were bacteria; later, this work was extended to plants and animals and much later – if we include gene therapy in this category – to human beings.
Transgenesis is the introduction of a gene or genes from one organism into another. This is a very broad deﬁnition and excludes natural ways of transferring genetic material, such as by mating or via viruses which carry foreign DNA or processes of DNA transfer taking place among bacteria or fusion between cells. It also excludes mating between different species. The techniques used for transgenesis are generally called genetic engineering and encompass isolating and preparing DNA, putting it into appropriate carriers called vectors capable of replicating in particular host cells, introducing them into host organisms, and analyzing the results. Sometimes the DNA is not isolated but synthesized from its building blocks or made by copying an RNA molecule into DNA. The recombined DNA is called recombinant DNA. The transgenic organisms are also known as genetically modiﬁed organisms (GMOs). Finally, it is necessary to clarify that cloning animals by methods similar to those used for obtaining Dolly the sheep is not transgenesis.
The fundamental problem in the early period of genetic engineering when the only transgenic organisms were bacteria was fear of creating a Frankenstein monster which could cause havoc by disrupting the teleological relationships among living organisms and humankind. At the time, it was known that the genetic code was universal. There was a fear that if, for instance, an animal virus known to be carcinogenic was placed in a bacterium, this could lead to a cancer-causing bacterium.
What was not known at the time, and only became apparent as the result of the numerous experiments performed in the 1970s and 1980s, was that even though the genetic code is the same in essentially all organisms, as is the general way it is read, the details of the way genes are read and regulated are very different in bacteria and in organisms which have nuclei. Thus, putting a fragment of human or viral DNA into a bacterium will not –unless special procedures and vectors are used – yield any useful or harmful product. Moreover – as was shown by cloning and analysis of various DNA fragments from mammals and mammalian viruses – very many animal and plant genes are not continuous, but the sequences coding for proteins are interrupted by noncoding sequences, called introns, which have to be removed before a protein can be made; this occurs on the level of the primary product of gene expression called RNA. RNA is the matrix on which proteins are made. Introns cannot be cut out by bacteria, and the probability of creating something harmful was found to be practically zero. This scientiﬁc truth – if left unchallenged by new strands of epistemic breakthroughs– therefore offers a means of assuaging some of the ethical concerns associated with transgenesis.
The second problem is quite broad and relates to whether or not humankind have the moral impetus to do whatever they please with other organisms in nature. While there have been little or no ethical concerns with bacteria and simple nucleated microorganisms such as yeast, the creation of new microorganisms is morally problematic. In this vein, the term “playing God” has come to the fore to describe how scientists increasingly usurp the “natural order.” However, the social and medical relevance of products of genetic engineering such as human insulin and growth hormone has contributed toward assuaging fears over harmful genetically modiﬁed microorganisms. This has also generally shaped the widespread acceptance of other genetically modiﬁed – transgenic – microorganisms and their products.
The problems concerning transgenic plants have been more of acceptance of altered food and the possibility of uncontrolled dissemination of such altered plants into the environment. The fear of organisms with extra genes is probably still the underlying cause of the lack of acceptance of transgenic plants which is quite common in Europe, in spite of the enormous amount of work performed by the European Food Safety Authority (Devos et al. 2014). This is not a problem in the USA, where transgenic soy, corn, cotton, papaya, and other plants constitute a high percentage of these crops. How this arose historically is an interesting question, but perhaps part of the answer is the lack of understanding in that all living things are made up of DNA. This seems to have become a problem even in the USA, where a recent University of Oregon poll indicated that 80 % of the responders were in favor of mandatory labeling of all foods containing DNA! (http://agecon.okstate.edu/faculty/publications/4975.pdf).
The problem with transgenic animals was and is somewhat different, as it mainly concerns the questions of what we may or may not do with animals, and in most cases is not unique to transgenesis. The extent to which we may use animals for our own purposes, be they very basic such as for food and clothing or very subtle such as models for understanding and treating human diseases, did not change qualitatively with the appearance of transgenic animals. Neither did the belief that the closer an animal is to humans, the more cautious we should be in deciding what is and what is not permissible (Olsson and Sandoe 2010).
Innumerable models of human diseases mainly in transgenic mice have led to a much better understanding of how these pathological processes take place, and even though many of them still cannot be cured, considerable progress has been made. In the last years, gene therapy in humans, which is an example of transgenesis, has enjoyed some successes. The general consensus on gene therapy is that if the introduced therapeutic gene cannot be passed on to future generations, there is essentially no ethical problem. However, there would be one if the therapy were applied to germ line cells. Currently, the methods of transferring genes for the purpose of gene therapy do not allow thinking about this possibility in any near future, but technical problems – unlike ethical ones – are sometimes solved very rapidly by some unforeseen breakthrough (Kimmelman 2005).
The fear of creating Frankensteinian monsters aroused by the formation of early genetically modiﬁed organisms in the 1970s has partly disappeared and partly has been transferred to the fear of transgenic plants as the basis for the foods that we eat. Though years of investigations on transgenic plants have not brought any data that consuming them could be in any way harmful, some fears still persist.
The ethical dimension of modifying our environment and the organisms which surround us has not been changed by transgenesis; man has been modifying and selecting animals and plants for a very long time, and practically nothing – with the exception of organisms living in wild environments – has been left as it was. While new techniques have made modifying plants and animals simpler, the question of what we can or cannot do to animals has become somewhat broader, but it is the same fundamental question which existed a long time before genetic engineering and transgenes is were introduced.
- Berg, P., & Mertz, J. E. (2010). Personal reﬂections on the origins and emergence of recombinant DNA technology. Genetics, 184, 9–17.
- Berg, P., Baltimore, D., Boyer, H. W., Cohen, S. N., Davis, R. W., Hogness, D. S., Nathans, D., Roblin, R., Watson, J. D., & Zinder, N. D. (1974). Potential biohazards of recombinant DNA molecules. Science, 185, 303.
- Devos, Y., Aguilera, J., Diveki, Z., Gomes, A., Liu, Y., Paoletti, C., du Jardin, P., Herman, L., Perry, J. N., & Waigmann, E. (2014). EFSA’s scientiﬁc activities and achievements on the risk assessment of genetically modiﬁed organisms (GMOs) during its ﬁrst decade of existence: Looking back and ahead. Transgenic Research, 23(1), 1–25.
- Kimmelman, J. (2005). Recent developments in gene transfer: Risk and ethics. British Medical Journal, 330, 79–82.
- org. The nobel prize in chemistry 1980. Retrieved from http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1980/
- Olsson, A. S., & Sandoe, P. (2010). “What’s wrong with my monkey?” Ethical perspective on germline transgenesis in marmosets. Transgenic Research, 19, 181–186.
- Mepham, B. (2005). Bioethics. An introduction to the bio- sciences. Oxford: Oxford University Press.
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