CHE391L/S14/Ethics

=Ethical Controversies in Synthetic Biology=

There are two main goals one must strive to achieve in an experiment in order to maintain high ethical standards: beneficence and nonmaleficence (Belmont Report). In order for an experiment to be considered ethically permissible, it must be both beneficial to individuals and society, and must not have reasonable possibility of becoming malicious towards an individual or society. These two standards come from the Belmont Report, a set of standards a researcher must hold themselves to when doing research on human subjects. While synthetic biology experiments are usually done on plants or bacteria, the main cause for ethical concern almost always stems from the human interaction with the GMO. In every facet of what we do as experimental scientists it is important to analyze the ethical concerns that many members of society hold in regards to synthetic biology, and, most importantly, hold ourselves to a high level of personal ethical standards. One must develop a sense of what sort of conduct a person should hold oneself to and expect of fellow researchers in the field. #Balmont1974

RNAi Insecticidal Crops
In 2006, Craig Mellow won a Nobel Prize for a process he developed to silence genes. This development was intended for use in curing a variety of diseases. His technique, however, has been implemented as a sort of genetic pesticide. In nature, the protein Dicer breaks apart RNA it perceives as foreign, which in turn tags complementary RNA in order for it them to be destroyed by other cellular components. By introducing non-viral RNA that corresponds to a gene found in the insect eating the plant, however, the cells in the insect are essentially tricked into committing suicide. This functions well as a pesticide, but there may be hazardous side effects. In 2012 Chen-Yu Zhang published an article in Nature stating that small RNAs from plants were detected in the blood of mice and humans after being consumed. This is troubling, for it the findings get confirmed, it is possible that by consuming these genetically modified plants could cause human cells to be tricked into killing themselves. Researchers at the Monsanto corporation, who are said to most “likely be the first to sell RNAi-based pesticidal seeds to farmers” (Kupferschmidt, 2013) say Zhang’s findings could be due to lab contamination and also note that humans would have to eat 33 kilograms of cooked rice per day to mimic what mouse diet in the study. Zhang’s findings were also unable to be mimicked in a study done at Brigham and Women’s Hospital and another at Johns Hopkins University School of Medicine, as both “studies combined show that there is negligible uptake of microRNA from diets in mammals” says Kennith Witwer (Kupferschmidt, 2013). The public, however, is still skeptical due to Zhang’s findings, and in order to bypass this scientists are attempting to develop a system by which the same pesticide is used by adding dsRNA to water and spraying it on crops. Kupferschmidt notes that “the fact that plants aren’t [Genetically Modified] might make this approach an easier sell.” This is an important statement to think about, as both ways of implementing this type of pesticide will cause humans to ingest the RNAs, however the latter does not genetically modify the crop, but still causes the RNAs to be present in the food. It is important to weigh whether it is ethical to, in essence, trick the public in believing they are not eating food grown with this pesticide, without them coming the their consensus that it is ok to eat. #Kupfershmidt2013 #Lundgren2013

H5N1 Possible Pandemic
During the bird flu crisis, two papers came out detailing how the H5N1 virus, when mutated, had the ability to pass between mammals via airborne routes. The first study, done by Yoshihiro Kawaoka at the University of Wisconsin in 2012, created a hybrid virus by combining an avian (“of, relating to, or derived from birds” - Webster) H5N1 strain with seven DNA segments found in the H1N1 virus. His study showed that it took only four mutations for the virus to be transmissible through air. The second study, published by Fouchier 10 months later in Science, found that it took at minimum 9 mutations for the virus to become transmissible by air. What is interesting about the politics that went into determining these results, is that Fouchier’s discoveries were not published for 8 months because the U.S. National Science Advisory Board for Biosecurity unanimously told Science not to (a decision which was reversed a few months later after viewing an extended version of the paper). While it is important to ensure that the good data has been collected before making the public worry, it is also important that the public remain informed. There was even international debate over whether the results should be published at all, even though the general gist of the results (that the H5N1 virus could become airborne) were bolstered by the paper by Kawaoka months prior. Many hold the position that the experiments should not have been done at all. They argue that although the studies could provide insight as to how the H5N1 virus could mutate and cause a pandemic, the experiments themselves produce the pandemic version of the virus. If the virus escapes the lab, then it could initiate the next pandemic. Yoshihiro Kawaoka published an article in nature during the heat of this debate stating that in order for pandemics to be prevented in the future, scientists need to continue work to study them now. #Herfst2012 #Enserink2012

Synthesis of Poliovirus
In August of 2002, Jeronimo Cello published an article in Science detailing how he was able to synthesize the complementary DNA to the poliovirus, and then infect tissue cultures with the virus. This experiment could be seen as disconcerting since it makes it possible for a virus that once caused a major epidemic to reappear and spread once more. The paper ends with a statement on the ethics of performing the study including its beneficence and nonmaleficence. “As a result of the World Health Organization’s vaccination campaign to eradicate poliovirus (23), the global population is better protected against poliomyelitis than ever before. Any threat from bioterrorism will arise only if mass vaccination stops (23) and herd immunity against poliomyelitis is lost. There is no doubt that technical advances will permit the rapid synthesis of the poliovirus genome, given access to sophisticated resources. The potential for virus synthesis is an important additional factor for consideration in designing the closing strategies of the poliovirus eradication campaign.” This statement is logical, as it is saying that bioterrorists will be able to bread the poliovirus, so it is beneficial to society for researchers to study the poliovirus, how it can be made, and perhaps investigate possible mutations that could cause it to overcome human immune responses that develop due to the vaccine. #Cello2002

Golden Rice
A case in which public concern or fear of GMOs had very negative consequences. In 2004 a genetically modified version of rice called “Golden Rice” was first grown in fields. The rice has a property that makes it unique, mainly it is a very good source of Vitamin A. This is important, as one of the main causes of blindness (among other diseases) in developing countries is due to Vitamin A deficiency. The people of many countries in east Asia, such as China, have diets that consist of large amounts of rice, and thus by growing Golden Rice, Vitamin A deficiency can be cured. In 2012 researchers from Tufts University visited China and gave the rice to children. Greenpeace China, an anti-biotech organization, accused them of not giving enough information to the parents in regards to what their children will be eating. After a year of investigation, Tufts University agreed that the study was not done in compliance with Chinese regulations as the researchers did not inform the parents that the rice had been genetically modified. As a result, Guangwen Tang, the head researcher in the study from Tufts, has been banned from conducting experiments on humans for the next two years, after which he will only be allowed to conduct the experiments under direct supervision. #Charles2013 #Goldenrice2014

iGEM
The UGent iGEM team in 2013 wrote about ethical issues in synthetic biology, and summed up the ethical concerns into a three categories: Biosafety (and Biosecurity), the ethical concerns of creating life, and whether it is acceptable to have intellectual property rights over a type of life. To summarize their stance, they hope that countries will engage in biosafety properly (specifically Europe), they are undecided on the ethics of creating life, and they essentially said that it is more practical to allow intellectual property rights. They also talked about the public opinion on synthetic biology, and said that there should be more communication between scientists and the public. UGent2013

Conclusion
Communication between scientists and the public could be beneficial to society (and would prevent future malicious situations such as the Chinese situation with Golden Rice). There are many topics in synthetic biology that take a lot of effort to understand, which most people do not go through the trouble of putting forth, and further can be difficult to explain to a society in which many have yet to even understand evolution. Yet if we are to progress, there cannot be this knowledge barrier between the public and scientists. The public does not know what the potential health effects of GMOs are, and while there have been a lot of studies that have conclusively found certain GMOs to be safe for consumption, as scientists it is oftentimes a good to hold a position of uncertainty and skepticism. Perhaps a more likely hazard that may arise is the possibility for many experimental results may be used in bioterrorism. If the genetic sequence for Polio and perhaps other long extinct viruses or diseases ends up in the wrong hands, then it could lead to the suffering of millions. Theoretically, however, by studying these diseases through synthetic biology techniques, scientists could develop cures or treatments for these diseases retroactively. In determining the ethical implications of an experiment, the idea of non-maliciousness, in addition to being considered in its own right, needs to be weighed against the potential benefits, as every invention since the wheel could be used for both good and bad.