CRISPR: The Break Down of DNA & Its Ethical Dilemma

Declared at an international level, the Geneva Protocol in 1925 incredibly impacted the stance with which major powers view the use of bioterrorism. There is in a sense the fear of unpredictable spread during warfare, and easy accessibility would create a war without clear opponents – that those who have produced biological agents may be able to keep their identities concealed, or even the identity of the mutation’s agent.

I was particularly interested in the CRISPR method, which is more or less a gene editing toolkit that uses an engineered bacterial protein Cas9 to manipulate RNA to target certain DNA sequences. Several critics claim that the creation of a “gene drive” goes too far, and after reviewing other articles about CRISPR, I found that a modified mushroom and type of corn have passed under the Animal and Plant Health Inspection Service, making them the first Cas9 crops. The reasoning is that CRISPR does not qualify under regulations, which calls to question the rate at which innovation is growing and the rate at which legislation passes to critically eye innovation. While there are critics calling CRISPR products “hidden GMOs”, there is also the belief that trying to regulate CRISPR will then hurt technological growth.

The greatest fear is not just the proliferation of bio-warfare in a target area and its unpredictability to spread; even more so, if there exist gene-editing toolkits with easy accessibility like CRISPR, this leaves room for adaptation by threatening states – states not within the Geneva Protocol or any form of multilateral agreement. And even more so, products to battle sickle-cell could mutate on their own – the unpredictability of changing a DNA sequence is hazardous, especially since CRISPR still does not take into account certain ribosomes and other microorganisms which could affect the DNA sequence. From my research, there do not exist studies of the long-term effects of CRISPR on DNA sequences, especially with exposure to the carcinogens of someone’s day-to-day.

While there is fear of over-regulating the potential innovations of CRISPR and similar engineering programs, the inability to tell between a modified organism (among other modes of CRISPR’s influence) makes me believe that it would be better to regulate the gene drive; that the government should recognize these new products – perhaps not as GMOs – but with some label and way of tagging CRISPR-linked products. Though the tag may stigmatize the application of CRISPR, it would certainly act as a precautionary. — Lucas

14 thoughts on “CRISPR: The Break Down of DNA & Its Ethical Dilemma

  1. A careful balance between innovation and ethics, the potential scientific gain that CRISPR offers must not cloud our judgement towards concerns for global health. As scientists explore the possibilities that CRISPR offers, perhaps they are doing so too hastily. I agree with Lucas that we should take pre-cautionary measures to fully understand the process before we dive into this new technology.

    The example that sticks out is one of the student testing the modification of genomes concerning lung cancer. The scary thought then appears of the worst case scenario: “a minor mistake in the design of the guide RNA could result in a CRISPR that worked in human lungs as well” thus infecting human populations as well (Ledford). As we study the implications of biological warfare, a highlighted risk is also placed on an accidental outbreak. The use of CRISPR without fully understanding the scientific process behind it poses a great risk of this natural outbreak occurring, especially so when the tools are relatively cheap and easy to use.

    However, with these fears laid out it is still undeniable the advancements that can be made through the now easier further experimentation of genomes. The use of gene drives to change ecosystems and eradicate possible diseases carrying populations is one that need not be ignored. The fact remains though that until we fully understand the long term implications of using CRISPR, it would be wise to err on the side of caution and loosely regulate it’s uses for now.

  2. I agree with both Jeremy and Lucas. In addition, the ease of making mistakes or producing results that lead to unintended consequences can also be linked to the new phenomena of “garage labs” that was discussed in Ledford’s other article, “Life Hackers.” Ledford explains about CRISPR, “This power is so easily accessible by labs–you don’t need a very expensive piece of equipment and people don’t need to get many years of training to do this.” Ledford previously details how, while the scientific community is wary of such garage labs, enforcing ethical and legal rules comes mostly from a “neighborhood watch stance.” Developing easy to use, cheaper tools such as CRISPR have a vast potential to transform the field, but it also makes it easier for the wrong people to get their hands on such tools. A balance between regulation and freedom is key to produce the desired results.

    I think it is also important to note that, when it comes to crops, while it is extremely important to encourage ongoing research and a wariness, like GMO crops, the most skeptical will most likely be consumers. Scientists generally regard GMOs as more safe than the average consumer will view them as. In my opinion, a labeling of gene-edited crops is most important for the future of research into the subject. Ledford emphasizes that gene editing makes it more difficult to tell the difference between genetically modified foods/genetically edited foods and the original. While GMOs do not have substantial research that would categorize them as less healthy or safe, having the ability to label genetically modified foods and genetically edited foods is crucial for research into the long term effects of such plants/animals.

  3. While I agree that the regulation of certain technologies that could do us harm—technologies like CRISPR—is beneficial in the long run, one could see how it is these very regulations are restricting the necessary information in order to utilize CRISPR in the safest way possible. It is this secrecy surrounding CRISPR and its harmful capabilities that will lead to more mis-managed experiments like the one conducted by Ventura (although he claims that he took the necessary precautions).

    The dual-use of synthetic biology—the idea that advances in biology could be used for either harm or good—is reminiscent of the problems the US faced upon discovering fission. What is particularly troubling, however, is the ease at which a working lab and the necessary components to work in synthetic biology are attained when compared with the necessary requirements for nuclear experiments.

    Especially with the rise of DIY (Do it Yourself) biology and garage labs, the legislation requiring registration and approval to work with potentially harmful nucleic acids and the like needs to be just as ubiquitous. Furthermore, as synthetic biology is regulated under a bunch of different federal agency’s—NIH, CDC, FDA, USDA…—one expects there to be overlap—but by the same logic, one can expect gaps as well in their jurisdiction.

    The government needs to be better organized in its regulation of synthetic biology and more forceful and dedicated in its implementation and advancement of algorithms that could detect potentially hazardous DNA sequences and other technologies to keep us safe. It needs to be able to adapt and advance as quickly as science itself.

  4. I think that the dual-use for genetic modification technologies such as CRISPR – as mentioned above – is important to delve more deeply into. As stated in the Nouri reading, “it is illegitimate to address biological weapons threats without also addressing key public health issues” (Nouri 452). Although the potential impact and devastation of a bioweapon or accidental outbreak is undoubtedly massive, the millions of people suffering from preventable diseases cannot be ignored. Which is more unethical: millions potentially dying due to a bioengineered pathogen, or the millions of people currently dying today due to malaria, cancer, and hunger?

    Nouri brings up an interesting point that the developed and undeveloped worlds need to work together to come up with a consensus for where to draw the line in biotechnological advances. Paradoxically, in the same way that restrictions on bioweapons serve global security for all nations, permitting the rapid advancement of biotechnologies in developed countries can be seen as a big step forward in combatting the current health security crisis faced by undeveloped countries.

    As we’ve read, the threat of a bio-engineered outbreak is less likely to stem from tightly regulated and controlled research facilities, but rather is more likely to come from the rapidly growing and unregulated community of DIY bio-hackers. Thus, restrictions on biotechnologies would hinder the progress of these advanced research facilities working to solve public health issues around the world. Biotechnology regulation is unlike nuclear regulation, where agencies can monitor the bottleneck of uranium and plutonium supplies and enrichment processes. Any ordinary person could unsuspiciously obtain the necessary equipment and material needed to start a bio-engineering laboratory in their garage (Ledford 651). Therefore, restrictive biotechnology policy at the same time would not be very effective against the decentralized and unorganized bio-hacker community. Thus, the question comes down to this: do we pursue policies which promote bio-engineered advancements in public health, or do we try to block these same advancements in order to try and regulate a decentralized, un-regulable network of bio-hackers?

  5. In general, I do agree with most of the previous comments concerning the need for regulation of new gene editing technologies like CRISPR. These new and emerging technologies have limitless potential, both positive and negative, to change the world we live in. However, following the discussion we had in class today I couldn’t help but wonder how difficult it would be to use CRISPR for bio-terrorism which is what was beginning to be implied towards the end of the question and answer period. While it was certainly clear that it was theoretically possible for an average person to set up a bio-lab in his garage for the purpose of bio-terrorism, I was unconvinced that this person would even consider using a technology like CRISPR, especially when it would be much easier to try and find some plague/smallpox-like virus to release on an unsuspecting population. Regardless of the bio-terrorism threat, however, there is still a serious need to regulate scientific experiments involving CRISPR because of their ability to inflict accidental nonetheless permanent side effects on entire species.

  6. When confronting the grave possibilities that dangerous scientific information arrives in the wrong hands, or a laboratory “mistake” causes an irreversible biological crisis, and considering potential regulations on bioengineering research, I believe that it is important for our policymakers and scientists to assume a defensive stance across the board. More specifically, all biological weapons research should be dedicated to the protection against an attack, making the public prepared in the case of an emergency, and vaccination techniques. Smallpox agents, for example, should exist for preventative research only, not to preserve the government’s ability to use the agent in retaliation for an attack. The most effective and morally sound way to respond to a biological warfare attack would be to prevent its spread with scientific innovation, not to retaliate with our own biological weapons. My argument in favor of defensive research only also applies to the recent advances with CRISPR and the rise of DIY biology. CRISPR technology should be used to fight off health problems and to develop cures, vaccinations, and pathogen-eliminating techniques, and not to create a new genomic phenomenon harmful to society, whether it be through pathogen creation or unwise human engineering.

    This defensive stance can and should be enforced at the governmental level through strict regulation of the larger, well-funded research facilities, as well as at the micro level through social pressure and self-regulation by fellow garage scientists. The United States, as a fully developed nation, has the opportunity to set the pace and direction of bioengineering research, and the ability to solve some of the world’s most pressing public health concerns. As a nation with immense international power, however, the United States also has the ability to initiate a biological weapons arms race if it were to take an offensive approach in its research. For nuclear weapons, the destructive power of the technology is so daunting that having access to a weapon essentially shields you from attack (i.e. mutually assured destruction), creating the incentive for nuclear arsenal build-ups. In contrast, the effects of biological warfare, though potentially disastrous, can be mitigated with the right scientific knowledge, such as vaccine or gene discoveries, and do not require a massive weapons build-up to ensure a nation’s safety. Instead, we can prepare ourselves with emergency measures and vaccines, making biological warfare an ineffective military technique for our enemies and decreasing the chances of it being used against us. In sum, biological innovation is potentially world-altering, but its power should be harnessed for defensive and protective purposes only, and to equip us with the knowledge necessary to resist the potential damage of bioterrorism, biowarfare, and natural pandemics.

  7. The concept of editing DNA and the accompanying ethical considerations were first realized with the development of recombinant DNA technology in the 1970’s. A group of scientists soon called for a moratorium on DNA research, in which most voluntarily obliged, while scientists and policy makers discussed the issue at a global conference. The deliberations produced the Recombinant DNA Advisory Committee of the NIH, a scientific peer review group, and guidelines that are still in effect or modified as technology progressed and risks became more well understood (Chapter 2, New Directions, 2010).

    With CRISPR on the loose, scientists are applying gene editing more rapidly than ever to complex problems such as climate change with biofuel-synthesizing microorganisms and new areas such as eliminating undesirable genes in a population through gene drive. While the DNA editing concept is similar, the speed, accuracy, and low cost of the CRISPR tool reduce a previously substantial operating resource barrier to synthetic biology. The CRISPR innovation creates new possibilities and uncertainties beyond the scope of the current guidelines and the experience of the biology community. While scientific efforts to use this technology are likely for the advancement of public health, there still exists risks from unintended consequences and those with ill intent.

    Today’s lecture suggested that independent groups wishing to cause harm would be unlikely to go through the laborious process of constructing a custom-made pathogen through CRISPR and other synthetic biology techniques. However, there should still be regulations that have DNA-producing companies comply with order scans for probable matches to harmful pathogens to prevent easy access by independent groups. To address unintended consequences, another moratorium or limits on experiment classes may be required to slow the current pace of adoption and truly evaluate the areas and experiment classes that are worth the risk of human catastrophe, and conduct approved research beyond those areas to methodically reduce the uncertainty of CRISPR impacts. Companies born from the CRISPR revolution such as CRISPR Therapeutics focus on delivering value through their strategic partnerships against diseases with pharmaceutical companies and should not be hindered by the limits.

  8. In an earlier post, the following hypothetical question was posed: “Which is more unethical: millions potentially dying due to a bioengineered pathogen, or the millions of people currently dying today due to malaria, cancer, and hunger?” I feel the need to answer this question because I came to a conclusion that I think the author was not trying to illustrate. I would argue the former is far more unethical by virtue of the fact that those diseases and health conditions were not given to the people as a direct result of human action, whereas the impact of a bio-weapon or an accidental outbreak is directly attributed to human action/error. Thus while there are definitely benefits from the groundbreaking research of CRISPR, regulation must be in place in order to ensure the safe and adequate study of the unintended consequences. For that reason, I definitely agree with Mary Claire that policy and research on bioweapons should be entirely preventive. Previously stated in this post and in the guest lecture, the threat of bioweapons being accidentally released or having unintended consequences from not being studied adequately seems much more likely than the threat of bioterrorism using weapons created by CRISPR. I too was convinced by the guest lecturer’s argument that we do not need to worry about terrorist’s enhancing or generating a new virus because they can simply use existing ones and still can kill as many people.

  9. If anything, I think the scientific community especially and the world generally should make efforts to further promote research in GMO’s and gene-editing technologies, especially with regards to how they can help. For example, crops that can resist certain insect species without needing pesticides, or things such as the round-up ready crops, are big advancements to help combat world hunger. Much of the big mysticism surrounding these products is due to how inaccessible it and information around it is to most people. It seems as if one big company, Monsanto, is pulling all the strings and making food unsafe without anyone knowing. If there were PSAs or other methods to spread the truth about GMO technologies, it could spread in a safer way than the “garage labs” that Mikaela mentioned, and could start to tackle some serious issues.

    Yes, as others mentioned, there are risks, however the amount of control over the product that gene-editing technology gives you opens up a whole new world of problem-solving, and should not be shied away from. We should instead invest the necessary attention, manpower, and capital so that we might see just how much these technologies have to offer. I also agree with Mary Claire’s point that the use of CRISPR technologies to defend against biological warfare as well as cure diseases is important, but am confused by her fear of “unwise human engineering” that might be harmful to society. I think there are ways that CRISPR technology could vastly improve our quality of life, and I look forward to those options being explored.

  10. The invention of CRISPR has revolutionized synthetic biology and the heightened potential for biological warfare. Amazing, positive developments in vaccines, disease eradication, cures, etc. lie with CRISPR, but the potential for significant hazard is also great. Because of this opposing dichotomy between CRISPR’s benefits and risks, government officials and scientists face problems of 1) identifying, 2) passing, and 3) implementing safeguard procedures to lower these risks.

    Bypassing the first problem of identification, I would like to focus on the concerns with passing risk-reducing legislation. In his post, Lucas makes an important point – “CRISPR does not qualify under regulations, which calls to question the rate at which innovation is growing and the rate at which legislation passes to critically eye innovation.” In the reading on “Biotechnology and Biosecurity,” authors Nouri and Chyba name one of the two severe challenges of regulating biotechnology as the “mismatch between the rapid pace of biotech advances and the comparative sluggishness of multilateral negotiation and regime building.” While radical biotechnological advancements, like CRISPR, are being rapidly developed, naturally lethargic government legislation is having a tough time catching up. Though there is ongoing debate about what the proper legislation for biotech developments like CRISPR should be, there is also a problem of installing these procedures in the first place. It may be necessary for expedited means of legislation to be put into place, perhaps with a designated legislative body/committee dedicated to solely overseeing biotech developments and passing relevant measures.

    The second greatest problem, I see, is the implementation of the measures that do pass. With a multitude of garage labs popping up alongside established university/government laboratories, there is a real issue with tracking the behavior of all biotech parties. To better implement legislative measures, I would advise a reduction or restraint on non-government/university/corporate labs (i.e. garage labs). In accordance with several of my classmates, I see the biggest biotech threat to public safety lying in unsupervised “garage labs,” as discussed in “Life Hackers.” Amateur biotech enthusiasts, who are less familiar with strict lab procedures found in a university/government setting, pose a reasonable threat in accidentally releasing hazardous material.

    However, while restricting these types of DIY scientists may be the wisest policy choice regarding reducing the chance of an accident, such a measure may have difficulty surviving through the legislative process. In America especially, we are forced to examine the ability of the government to infringe upon their private activities; in this case, I pose the question, to what extent can the government impose if it’s for the public health of the people?

  11. There has been a lot said about the ethical dilemma of biotechnological progress that CRISPR brings, and I think that all of your reasonable disagreements show that there is likely no single, perfect answer to the question of regulation, or the degree to which the technology must be regulated and monitored. However, this ethical dilemma becomes both more complicated and more charged with news of attempted changes made to human DNA, which could possibly yield both the most beneficial advancements in the forms of cures and treatments for medical ailments, and the most dangerous threats to human society in the forms of new pathogens. While on the one hand, a researcher could potentially find a cure or treatment for a terrible, widespread disease and bring happiness and hope to innumerable people, it is also possible that either a hostile entity with a gene drive could find a way to introduce a gene that could cause infant fatalities if handed down to the next generation (hereditary SIDS).

    Mikaela mentioned that consumers, and the general population, tend to be skeptical of GMO’s, while scientists tend, as a group, to accept them as safe. It seems to be a human tendency to at most dislike and at least distrust things that you do not understand and are unfamiliar with, and if GMO’s could cause such a reaction imagine what reaction editing human genomes would elicit. The issue that CRISPR raises is that it amplifies this fear of the unknown and not understood; it spreads the ability to edit gene sequences beyond the conventional population of those who would do that (researchers, doctors, virologists, etc) to anyone curious enough (and with equally unknown intentions) to purchase equipment that can be found on Ebay for a few hundred dollars, as mentioned in “Life Hackers.” Furthermore, CRISPR is not only easy, it is also powerful: it makes it possible to alter sequences and with a 97% accuracy rate observe the mutation in the next generation, as seen in the Bohannon article in Science Magazine.

    It is very understandable, for these reasons, that the public would be indisposed to trusting the spread of CRISPR technology to untold more people. However, I need to say that, despite public antipathy, not only is the free exchange of ideas absolutely central to scientific progress, but competition and capitalism have proved incredibly if not the absolute best incentives to scientific progress, and to limit these exchanges or to put up barriers to trade these ideas would greatly slow potential advancement. I do not in any way maintain that this means that there should be no regulation at all; I am simply taking a slight reversed perspective than I observed in previous comments; rather than see what we should allow to pass through regulations, we should think carefully about the regulations to put in place concerning CRISPR technology.

  12. This is a class designed to focus on the threats science can pose to global security. We are not focusing on the benefits, as a molecular biology class might. I think this is an important bias of this class that we need to keep in mind as we think about regulation, control, and restriction on the use of CRISPR. The positive, life-saving and life-improving possibilities for CRISPR are essentially boundless. And while it certainly has unknown and potentially dangerous consequences, as you all have thoroughly laid out in your answers, the positive potential is well-known. We don’t have the information yet to know how harmful CRISPR might be. Scientists should be working on trying to figure that out, and they should certainly be taking precautions while working with the system. But this shouldn’t dissuade people from working on this research. Good science policy in this case involves funding, supporting, and encouraging both the positive, public-health-affecting research and the negative, public-safety-affecting research. I, for one, am inclined to believe that this will eventually be proven a net positive scientific discovery. But we won’t know until both sides of the balance sheet are filled out.

  13. Reading about CRISPR has most reminded me of the “black ball analogy” in that each scientific tool researchers discover, they are not sure if the implications will be ultimately detrimental or good for society. I believe that the development of CRISPR is an important one in our world and furthermore, that access to the technology cannot be limited to only certain parties but must be made public to all. That being said, there are still strong ethical and prevention concerns. Firstly, the ethical ones stem from CRISPR’s ability to completely eradicate a genome sequence. When reading John Bohannon’s “Biologists Devise Invasion Plan for Mutations”, I was concerned with the scientists unpreparedness for the reaction they incurred. When they changed the entire population of flies to contain the mutation that was otherwise only supposed to affect 25 percent of the population, the massive implications of CRISPR became real. One could change entire populations- and what is more- he or she would be unable to reverse the changes they inflicted. In class we talked about the inclusion of a “kill switch”- and the idea, although terrifying, seems necessary. Essentially all genetic sequencing would have to then also include a way to kill the organism if something went wrong. For instance, a scientist could create a sequence that made all organisms die if they were then introduced to a specific pathogen or combination of elements.

    Another important part of CRISPR is that it it not yet deemed completely safe. In Heidi Ledford’s “CRISPR, The Disruptor”, she notes that scientists still have to insure that the technique does not cause damage to other sequences within the organism. So while it may eradicate certain unwanted sequences, it might be affecting healthy ones. There is still a lot of testing that needs to go into the process, but admittedly, it has already done some good. For instance, its ability to create disease- resistant crops seems extremely promising as that could help areas were crops are dying. Perhaps there could be a way to create crops that can sustain on less water, so areas with drought can also be aided. The implications of CRISPR are infinite, and yet scientists do need to tread cautiously as one wrong sequencing and a population could change in the blink of an eye.

    On a final note, an important aspect that must come along therefore with CRISPR, and as noted by Lucas, is a form of regulation. As Lucas mentioned, the government should not restrict too firmly the technology but should create some form of regulations such that all people have a common understanding of the appropriate use of CRISPR. I think the government , however, unlike what Lucas thinks, should be overly-cautious with the technology. As we learned in class that biological development is occurring even faster than Moore’s law, I do not see the harm in slowing it down and really thinking about the implications of the steps we are making. We can not turn back time, and the technology we discover is here to stay- so we should be sure it is being developed under the right restrictions.

  14. Like many of my fellow students, I would like to see more formal regulation of the biotech industry. Without impeding scientific research, it would be possible to codify some informal regulations already in place – such as private companies’ screening of DNA sequencing requests. Additionally, as Nouri and Chyba mention in “Proliferation-resistant biotechnology,” technological innovations and international cooperation would go a long way in increasing oversight of the potential creation of pathogens.

    While I recognize the need for regulation and the difficulties that arise from such a rapid rate of technological innovation, I am less concerned about CRISPR-related accidents. CRISPR is quickly becoming an essential tool in the fight against infectious diseases and should not be stigmatized. I am not necessarily against labelling CRISPR-developed food products: there is no reason to keep consumers in the dark. However, I do not believe that this labelling would be particularly helpful. Some consumers may avoid CRISPR products as they do other GMOs but with equally no benefit to their health.

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