Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 Asilomar Conference on Recombinant DNA 1975 Dear Delegates, It is my pleasure to welcome you all to the Asilomar Conference on Recombinant DNA – a 1975 meeting of scientists, journalists, lawyers, and government officials which changed the course of biological engineering. My name is Ranjani Parthasarathy and I am thrilled to serve as your director. I would like to open with a brief personal introduction. I am a second-year student here at the College, and I am majoring in Biology and International Relations. I love learning languages, and I’m living in the Spanish House this year – I hope to be familiar with basic Arabic and Turkish before I graduate In addition to being part of the W&M International Relations Club (which runs WMHSMUN), I’m also a member of the Rowing Club, a co-founder of our Classical Indian Dance team (Haasya), and the Historian for the Undergraduate Honor Council. Turning to the specifics of the Committee: this will be a fascinating take on the meeting of minds which set informed guidelines for biological research involving recombinant DNA. Each of the topics elaborated upon below critiques a different facet of the challenges faced by a researcher in this field. Ranging from far-fetched scenarios like the engineering of a dangerous, antibiotic-resistant Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 bacterium which somehow escapes from the lab, to more hotly contested topics such as the engineering of DNA from humans or other complex organisms, this Conference promises to place a variety of viewpoints in close contact and encourage lively debate on scientific issues. WMHSMUN requires that every delegate submits a position paper. This paper must address the topics presented by the committee through the lens of your position. For more information on what is expected from position papers, there is a link on the WMHSMUN website, under the “committees” tab. We highly suggest that you use this tool in order to make your position paper as effective as possible! For Specialized Agencies, we highly encourage you to email your position paper to your chair before the first committee session. If this cannot be done for any reason, you may submit a hard copy to your dais at the beginning of the first committee session. If you have any questions about the Committee after reading this background guide, please feel free to email me. I look forward to seeing what each delegate proposes and what you all can accomplish together over the WMHSMUN XXX weekend! Ranjani Parthasarathy Director, Asilomar Conference on Recombinant DNA 1975 [email protected] Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 I t is the year 1975, and molecular Introduction biologists & Background throughout Information the developed world have voluntarily paused experimentation involving recombinant DNA due to fears concerning these uncharted waters1. The Asilomar Conference on Recombinant DNA is being held in sunny California to address concerns in the scientific community regarding the scientific process, morality, and safety in this new field of research. DNA, an initialism of deoxyribonucleic acid, is itself foundational to life. Often referred to as the ‘blueprint of life,’ it exists in every living organism2. The central dogma of life, as stated by Watson and Crick after their landmark discovery of the structure of DNA, explains the flow of information as starting as genetic information, DNA, then being transcribed into an intermediate molecule, RNA, and finally becoming realized as proteins.3 1 “The Recombinant DNA Debate,” North Dakota State University, accessed July 19, 2016, https://www.ndsu.edu/ pubweb/~mcclean/plsc431/debate/ debate3.htm. 2 “DNA: the Blueprint for Life,” National Information Society Learnership in Ecological Informatics, accessed July 19, 2016, http://planet.uwc.ac.za/nisl/ biodiversity/loe/page_08.htm. 3 “The Central Dogma,” Cold Spring Harbor Laboratory, accessed July 19, 2016, Discovery of DNA Despite its ubiquitous presence in the field of biology today, the first person to take an interest in isolated DNA was a chemist: Friedrich Miescher isolated “nuclein,” DNA molecules, from pussoaked bandages in 18694. When its chemical composition was uncovered, however, it seemed far too simple to serve as the design for the vast variety of organisms that comprise the biosphere. Proteins were first thought of as being the true information underlying life, due to their unique structures and functions. Nevertheless, the unraveled structure as proposed by Watson, Crick, Franklin, Wilkins, and Donohue hinted at the true complexity of this molecule5. The ability of DNA to self-replicate – as each side can serve as a template for the creation of the other – is the basis of heritable change, making recombinant DNA all the more potent as a technology in this modern era. Recombinant DNA The technological advance that has prompted this forum is that of recombinant DNA. Recombinant DNA technology allows small fragments – generally genes, the units of DNA https://www.dnalc.org/view/15876-thecentral-dogma.html. 4 “The DNA Story,” Royal Society of Chemistry, accessed July 23, 2016, http://www.rsc.org/chemistryworld/ Issues/2003/April/story.asp. 5 Ibid. Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 which code for specific proteins – of foreign DNA to be integrated into a host chromosome. These recombined genes are then expressed; that is, the desired proteins are produced by the host organism6. It has been pioneered in bacteria: with the bacterial chromosome, or total DNA, serving as the majority of the DNA present in the recombineered bacterium, and single genes from other organisms as the DNA that is spliced into the now-transformed organisms. In considering this technology, it is not insignificant to note that at the rate our knowledge is currently growing in this field, it would not be unreasonable to expect to have an understanding of the composition of the human genome itself by the turn of the millennium. Ethics and Evaluation Previous discussions about scientific research on this scale have been driven by animal rights groups outraged by the prevalence of animal experimentation in medical and chemical testing. They have led to the passage of national legislation which is considered by many to hinder the free advance of scientific research, and which is scientifically incomplete in according protections to, e.g., rats and mice but not birds or squid. One of the unstated goals of this convocation of scientists is to establish rational criteria for experimentation with and creation of recombinant DNA in a manner which will not restrict research but which will protect scientists and the public alike, to a degree which will forestall the creation of more restrictive legislation that would place an additional burden on researchers7. N otably, one experiment has already been Topic I: forestalled due to Containment concerns about the potential for transformed organisms to escape the laboratory. Paul Berg, at Stanford University, recently planned to splice SV40 into E. coli. Unengineered, Escherichia coli is a typically harmless species of gut bacteria that is well-studied and characterized. SV40, on the other hand, is less benign. SV40 is a simian virus (one which originally targets monkeys) which has been shown to cause cancerous tumors in both monkey and human cell lines8. The Berg lab has not stopped 6 “Herbert W. Boyer and Stanley N. Cohen,” Chemical Heritage Foundation, accessed July 25, 2016, http://www. chemheritage.org/discover/onlineresources/chemistry-in-history/themes/ pharmaceuticals/preserving-health-withbiotechnology/berg-boyer-cohen.aspx. 7 Rasmussen, Nicolas, “DNA Technology: ‘Moratorium’ on Use and Asilomar Conference,” eLS (2015), accessed July 26, 2016, doi: 10.1002/9780470015902. a0005613.pub2. 8 “The Recombinant DNA Debate.” Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 experimenting at this level; merely, they have postponed those experiments that have provoked the most discomfort among the scientific community. They have successfully transformed E. coli with plasmids that confer antibiotic resistance. In this context, plasmids are small loops of DNA (generally less than 1% of the size of a bacterial chromosome) that cannot replicate outside of their host organism. When successfully introduced into a host, they can both replicate and cause transcription and translation of the genes they encode. Berg’s lab has engineered plasmids that contain both the necessary genetic information to replicate in the host of choice and genes conferring resistance to a gauntlet of antibiotics, including tetracycline and kanamycin9. Indeed, Berg’s lab is at the forefront of recombinant DNA technology, and thus it is somewhat fitting that he has called for this conference. His lab has not restrained itself until it faced this public disapproval, successfully inserting genes into E. coli from organisms as different from bacteria as eukaryotes10. Notably, they have spliced in genes from the African clawed frog – a vertebrate used as a model organism for human-like early development. 9 “Herbert W. Boyer and Stanley N. Cohen.” 10 Ibid. 1. What are the implications of using common Questions to organisms, Consider: especially ones that are part of the human flora, as hosts for recombinant DNA experiments? 2. What safeguards can be put in place to prevent recombineered organisms from escaping a laboratory procedure? Should all organisms with any foreign DNA be treated with an equal level of caution, or are some more dangerous than others? 3. What are the long-term implications of engineering organisms with resistance genes? Should these implications lead to increased levels of precaution when conferring resistance upon pathogenic organisms, or will containing these recombineered organisms limit that risk sufficiently? 4. The public perception of recombineered organisms running amok is perhaps the most dangerous obstacle to progress in this field. What safeguards can be designed to lessen public fear, and how can they be maintained without increasing the burden on researchers? Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 I n just twenty years since elucidation Topic II: of the structure of DNA, biotechnology Bioethics has developed at an unprecedented rate. Even with the crudeness of DNA editing offered by current techniques, there are already accusations that scientists are ‘playing God.’11 Indeed, splicing DNA is the first step to being able to narrow down which segments are truly essential to life, and which are less necessary12. Furthermore, as scientists have already shown, all organisms are susceptible to this kind of editing. Imagine one future where correctional editing can prevent diseases like sickle-cell anemia, which is caused by a single amino-acid substitution as discovered in 1958.13 Imagine another future, perhaps, where vertebrate embryos whose genes were wrongly spliced are born misshapen and 11 Austin, Charles, “Ethics of Gene Splicing Trouble Theologians,” New York Times, July 5, 1981, accessed July 29, 2016, http://www.nytimes.com/1981/07/05/ us/ethics-of-gene-splicing-troublingtheologians.html. 12 Lewis, Ricki, “Craig Venter’s Synthetic Genome 3.0 Evokes Classic Experiments,” DNA Science Blog, March 24, 2016, accessed July 12, 2016, http://blogs.plos. org/dnascience/2016/03/24/craigventers-synthetic-genome-3-0-evokesclassic-experiments. 13 Ibid. malformed in the laboratory. Is this but the cost of science?14 Closer to the present, Lysenko’s theories regarding inheritance and cytology have destroyed the Soviet Union’s advancement in biology.15Nevertheless, the kinds of heritable adjustments to genetic expression that he desired may become possible. Keeping in mind that traditional farming practices are merely accelerated evolution and that, in some sense, recombination (using naturally occurring enzymes, as it does) might be viewed as the next step: consider ideas as far-flung as genetically edited agricultural produce or weight-loss pills that promise to change the way one’s gut bacteria digest food. There are more than simply these possibilities; this committee may consider some or none of the situations proposed here. The Animal Welfare Act (AWA), passed by the U.S. Congress in 1966, may offer some precedent in this situation.16 14 Zoloth, Laurie, “Bioethics and Genetic Research: Selected History and Essential Premises,” Office of Science Policy, NIH, accessed August 3, 2016, http:// osp.od.nih.gov/sites/default/files/13_ Bioethics_Zoloth.pdf. 15 Joravsky, David, The Lysenko Affair, Chicago: University of Chicago Press, 2010, https://books.google.co.in/books?id=nWVBgEyiiMYC&printsec=&hl=en. 16 “Laws and Regulations,” New England Anti-Vivisection Society, accessed August 4, 2016, http://www.neavs.org/research/ laws. Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 Regulating the use of a variety of mammals, which are considered to sense pain and to have some sentience, the AWA established the necessity for an institution-level committee which would serve as a control on profligate waste of animal life and suffering. This committee is composed of community members as well as professional researchers and veterinarians, who bring their various expertise to determine whether an experiment is ethically designed. This group seeks to avoid the public outcry which necessitated the passage of the AWA by preempting doubts about ethical experimentation with scientific standards and safeguards. 1. What are ethical concerns associated with Questions to working with Consider: vertebrate DNA, or even human DNA? How might they be addressed by the scientific community before government regulation becomes necessary? 2. What ethical decisions must be made regarding embryonic experimentation and methods of DNA acquisition? How can this group create institutional rules and protocols that will have room for future developments in this field? Who should oversee the implementation of these rules? 3. How might medical laboratory experimentation raise different concerns from experimentation by industry scientists, or commercial use of recombination to increase agricultural yields, and what standards could be put into place for each of these situations? Should they be regulated separately, or altogether? C ontinuing the parallels to animal research, Topic III: this body may Sourcing consider concerns about the forms from which recombinant DNA are drawn. Although more stringent restrictions on animal research pertain to more complex organisms (that is, organisms most similar to humans), the same guidelines may or may not be appropriate for recombinant DNA research. On the one hand, the length of DNA from viruses and bacteria is the shortest known, and thus could potentially be the most easily characterizable. Investigating DNA in this sandbox model could potentially lead to groundbreaking understandings which will revolutionize scientific study. Thus, leaving the fewest restrictions on this level of research would encourage research at this basic level and create a solid foundation of knowledge on which to build for more Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 complex experimentation. On the other hand, studying DNA from single-celled organisms in single-celled organisms poses perhaps the greatest risk, as these organisms – if viable – will be as self-sufficient as their wild counterparts. While DNA taken from a complex, multicellular organism will not be able to recreate that organism when expressed by a bacterium, DNA taken from another bacterium will undoubtedly have more of an impact on the host, and the host cell will already be a full organism. Of course, there are many more arguments for and against placing limits on rDNA research at any level – single or multicellular – than those discussed here. Some of those arguments concern the dangers of toying with already virulent organisms whose pathogenicity is harmful to humans, and the potential for misdevelopment of multicellular organisms due to errors introduced into their DNA.17 Ethical concerns effectively prohibit research from occurring directly on humans, and even after extensive animal testing, clinical trials are still undertaken with great trepidation. As-yet unexplored 17 Berg, Paul, Baltimore, David, Brenner, Sydney, Roblin, Richard O., and Singer, Maxine F., “Summary Statement of the Asilomar Conference on Recombinant DNA Molecules,” PNAS 72 (1981), doi: 10.1073/pnas.72.6.1981. is the question of whether DNA taken from humans should be approached with similar caution, or indeed whether DNA should be taken from humans at any stage of development. It is within the purview of this body to discuss in a civil manner the potential for future studies involving human genes, and to establish limits for the ways in which DNA may be acquired for these studies. Although the technology may not yet exist for DNA to be acquired in a manner consistent with those guidelines, the body will have the flexibility in future to revisit these rules as technology advances, and it is better to be prepared for the future than to be caught unawares.18 1. Guidelines for the use of vertebrates Questions to emphasize Consider: reduction, refinement, and replacement.19 Should those guidelines be extended to the DNA of vertebrate organisms as well? Should they apply to recombinant DNA, and if so, to the standards of the 18 Berg, Paul, “Meetings that Changed the World: Asilomar 1975: DNA Modification Secured,” Nature 455 (2008): 290 – 291, doi: 10.1038/455290a. 19 “Alternatives to Animal Testing,” National Institute of Environmental Health Sciences, accessed August 7, 2016, https://www.niehs.nih.gov/health/topics/ science/sya-iccvam. Asilomar Conference on Recombinant DNA 1975 // WMHSMUN 30 host organism, or to that from which the spliced-in DNA originates? 2. What are some concerns surrounding the ability of organisms to persist outside the laboratory, and how might sourcing DNA from different organisms play into earlier standards created by the containment guidelines? 3. How can guidelines be standardized across laboratories and countries, allowing fair collaboration and repeatability? How can foundational work be elaborated upon and how far should guidelines allow flexibility to account for future advances in technology and scientific knowledge? General References: 1. https:// en.wikipedia.org/ wiki/Asilomar_ Conference_on_ Recombinant_DNA
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