DNA Research Discussion Essay Assignment
(1) Address whether the NIH should fund rDNA research.
(a) State whether the NIH should fund rDNA research. Your answer could be yes, no, or somewhere in between.
(b) Provide details from the readings and/or lectures to support your stance.
(c) Identify one stakeholder (individual or institution) whom you believe would support the stance you have chosen.
(d) Tell us why you believe this stakeholder would hold your stance.
(2) Create a counter-argument.
(a) Use specific details from the readings and/or lectures to demonstrate a counter-argument to the stance you chose above.
(b) Identify one stakeholder (individual or institution) whom you believe would support this counter-argument.
(c) Tell us why you believe this stakeholder would support this counter-argument.
Policies for Genome EditingModule 4, Lecture 2
Title Slide Welcome to Module 4, Lecture 2: “Policies for Genome Editing.” In the last lecture, we learned some of the basics of policy and the policy analysis process, including major differences between policies, politics, and laws. In addition, we learned that stakeholder analysisis the core of policy analysis, and that it consists of continually assessing the four I’sofindividuals, institutions, interests, andinfluence. Finally, we learned that policy analysis includes problem identification,followed by policy formulation, adoption,implementation, andassessment.In this lecture, we will explore two case studies in the making of public policies for genome editing. Like in the history module, these include the advent of recombinant DNA in the 1970s and 1980s and the riseof CRISPR/Cas9 in the 2000s and 2010s. For each, we will build on the historical materials to consider how the policy process unfolded at each step, paying particular attention to the individual and institutional stakeholders and their interests and influences. We will end the lecture with lessons we can take away from genome editing that are relevant to science policies overall. So, let’s travel back to the 1970s once more, in this case exploring the policymaking process for recombinant DNA.
Slide 2: rDNA: Problem Identification & Policy FormulationNow, we have already addressed the process of problem identificationin the early history of rDNA policy. In the history module, we learned that the first rDNAs emerged from the labs of Paul Berg and Stanley Cohen of Stanford and Herbert Boyer of UCSF around 1973. We saw that these technologies arose from studies of bacterial systems, and that in the 1970s there were concerns regarding whether rDNA presented undue risks to the public and scientists and whether technologies derived from rDNA were patentable in the US. In 1974, biologists enacted a voluntary moratorium on rDNA research until the risks could be more fully assessed and the NIH could consider policies to help mitigate these risks. By the late 1970s, the moratorium had been lifted, concerns over biohazard had calmed down, and the patentability of rDNA inventions had been confirmed by the granting of the first Cohen-Boyer patent in 1980.Thus, this context provides us with the main problem for policy regarding rDNA in the 1970s. Scientists wanted to pursue the potential benefits of rDNA research, but the perceived risks were real, so biologists required policy guidance to move forward. We also learned in the history module that in 1976, the NIH issued the first version of its “Guidelines for Research Involving Recombinant DNA.” Yet, we stopped the story there for the most part. So, where did these policies come from, and how did they affect research? It is to these issues that we now turn.Perhaps the most important figure in the policy formulation process was Paul Berg, the biochemist who produced the very first rDNA molecules and whom we have already met. In 1973, at a research conference, a group of biologists including Berg decided that the advice of the National Academy of Sciences was imperative before rDNA work could continue. The
2National Academy of Sciences, or the NAS, is an advisory body providing advice to the federal government. In his capacity as chairman of the NAS committee convened to investigate rDNA, in 1974 Berg co-authored one of the readings for this week: an article in Sciencemagazine that laid out “potential biohazards of recombinant DNA molecules.” These hazards centered around the use of the bacterium, E. coli, as a vector for cloning rDNAs. Because E. coliresides in the human gut, the fear was that recombinant DNAs spliced into bacteria might escape the lab and share genetic information with bacteria in the human digestive tract, potentially resulting in the spread of new kinds of antibiotic resistant bacteria or even cancer-causing viruses. The main conclusions of the Sciencepiece were that a research moratorium was necessary; that even after the moratorium, scientists should be hesitant about making antibiotic-resistant plasmids that did not already exist in nature; and that an oversight committee, guidelines, and an international meeting of stakeholders were all necessary to discuss the next steps. Each of these things took place, providing the core of policy formulation for rDNA. We will focus on just the international meeting now, before moving on to policy adoption.In February of 1975, the International Congress on Recombinant DNA Molecules unfolded at the Asilomar Conference Center in Pacific Grove, California. The meeting received funding from the NIH and NAS and was organized by Berg alongside four other biologists, including Maxine Singer at the NIH. Now hailed as one of the most important meetings in the history of biology, Asilomar was convened to consider whether the moratorium on rDNA work should end and, if so, what mechanisms of containment should be recommended to reduce the risks of biohazards. This week, you will read about the strategies the Asilomar attendees agreed to in their 1975 “summary statement,” including the use of state-of the art fume hoods as physical blocks during research and special plasmids that could not replicate outside the lab.In addition, in this 2017 video by the NIH Office of Science Policy, we observe some of the Asilomar participantsdiscussing the biological issues in 1975. So, to summarize what we have learned thus far, the problem identificationand policy formulationphases for rDNA in the 1970s left several options for policymaking agencies such as the NIH to adopt, demonstratingthat science policies are both collective–they respond to competing interests–and historical, in that they respond to the needs of stakeholders at given points in time.
Slide 3: rDNA: Policy Adoption, Implementation, & Assessment
So, what did agencies such as the NIH do in response to Asilomar? And why is this case study relevant for genome editing policy today? Well, we can now return to the 1976 “Guidelines for Research Involving Recombinant DNA,” which appeared in the Federal Registeron behalf of theNIH on July 7, 1976. The cover page in the Registerappears on the right-hand side of this slide. As it turned out, these guidelines incorporated most of the consensus points the scientists had agreed upon at Asilomar, for instance with regards to biological and physical containment of rDNA-based hazards. In turn, the NIH reserved the right to withhold its funds from investigators not adhering to the guidelines, even if the guidelines did not have the force of law or statutory regulations such as those from the FDA. What’s more, in keeping with the 1974 “hazards” article and the 1975 consensus statement from Asilomar, the NIH Director established a Recombinant DNA advisory committee, known as the RAC, in 1975. The job of the RAC was to provide oversight ongrant applications and ongoing
3work, ensuring that all NIH-funded projects followed the guidelines. Working on the advice of the Asilomar workshop, members of the RAC authored the 1976 guidelines. The implementationand assessmentof the NIH guidelines,in turn, have been flexible and ongoing. The RAC itself existed until 2019, when the NIH disbanded it in place of the Novel and Exceptional Technology and Research Advisory Committee. This new committee provides the same functions as the RAC, but its jurisdiction includes a broader range of emerging bio-technologies such as CRISPR. The RAC and its successor have also always coordinated their oversight with the FDA in its regulation of human subjects research for the development of new medicines. This coordination continues to be a part of NIH policy, for instance with regards to the degree of oversight it has over Human Gene Transfer Research, or the transfer of genes into humans using rDNA. As for the NIH Guidelines, they continue to be revised given new methods and stakeholder concerns. And as shown on the left-hand side, in 2017 the NIH held a meeting to honor the continued relevance of the Guidelinesand solicit further stakeholder input, leading to a revision in April 2019. So, to summarize, science policies are flexible in addition to being collective and historical. Finally, in Berg’s 2008 review of Asilomar, you will read more about the stakeholders in the rDNA story.These included scientists, who wanted to continue work in this field but also to act ethically. People outside the lab were also stakeholders, as they stood to gain from the applications of rDNA but also to suffer in the events of biohazards. The many journalists present at Asilomar helped keep the public apprised, and some non-scientists attended the meeting. Finally, there was the NIH itself, the leaders of which aimed to advance public health without doing undue harm. Many of these lessons spill over into the making of policies for CRISPR genome editing, and it is to these that we now turn.
Slide 4: CRISPR: Problem Identification & Policy Formulation
So, how have public policies been made with regards to CRISPR genome editing? And how have these policies related to other issues, such as rDNA? As it turns out, many similarities exist between the two cases, even as problems related to CRISPR are still emerging and being hotly debated by scientists, policymakers, and the public. So, we will address the processes of problem identification and early policy formulationfor CRISPR first, before turning to the adoption, implementation, and ongoing assessment of policies for genome editing.Now, some of the policy problemsthat arise with CRISPR were also discussed in the history module. The scientific possibilities associated with the precise, reliable, double-stranded DNA breaks CRISPR makes possible are vast, as evidenced by Doudna and Charpentier’s Nobel Prize in 2020. Yet, as with rDNA, the full scope of the implications of applying CRISPR to human subjects is for the most part unpredictable. Thus, policy guidance is needed to proceed with certain types of research. In the US, as we saw in Jennifer Doudna’s 2015 TED Talk, biologists have called a moratorium until further notice on heritable human genome editing, presenting another parallel to rDNA. In addition, to address the policy problems and some solutions, a meeting was held. Doudna and two other biologists are shown at the right here at the first “International Summit on Human Genome Editing,” held in Washington, DC in 2015.At this meeting, the policy formulationprocess was advanced, as 500 people from 10 nations and 3000 more online convened with funding from the US National Academies of Science and
4Medicine, the British Royal Society, and the Chinese Academy of Sciences. A major output was the 2017 report on the left-hand side of this slide: Human Genome Editing: Science, Ethics, and Governance. In particular, Chapter 2 explores oversight of human genome editing and overarching principles for governance, including existing policy frameworksthat apply to new human genome editing technologies such as CRISPR.
Slide 5: CRISPR: Policy Adoption, Implementation, & Assessment
So, what is in this report? Well, the report clearly delineates between somatic, or supposedly non-heritable, and germline, or heritable, human genome editing, which we saw in Module 2. One of the most important conclusions is that existing policy and regulatory frameworks from the NIH and FDA will likely prove sufficient for the governance of most somatic applications of CRISPR. The report reminds us that the NIH’s original rDNA Advisory Committee, which was re-named in 2019, still fosters public discussion and oversight. The rDNA Guidelines apply, too. In addition, human subjects research including for gene transfer therapy and somatic gene therapy–which really means, any method of altering somatic genes–all falls under the FDA’s regulations. Thisis also true for research on human gametes, embryos, and fetal tissues, where the NIH has some oversight as well, for instance through its Guidelines for Human Stem Cell Research.Overall, however, as the Box 2-1 at the right here shows, the report concludes that 7 principles should govern human gene editing research, as new policies are implemented and assessed. These overlap with bioethical principles, such as the principle of due care, which states that all clinical trials should proceed with evidence and deliberation. The ethical principle of respect for persons, in turn, is the idea that all human subjects have equal moral value. Finally, as the NIH Director’ statement in 2015 noted, the NIH at this time is not funding research involving heritable human genome modification–in accordance with FDA regulations. The NIH is, however, funding research on basic biological and somatic cell applications of genome editing, and it keeps tabs on policy issues in a website shown on the left-hand slide of this slide. If we were to add more stakeholders to our discussion after studying the NIH’s more recent genome editing policies, these would include the FDA, which has statutory authority to regulate the products of gene therapy as drugs. Another stakeholder is the human research subject, who has protections under the law and stands to accrue benefit and/or harm from genome editing research.
Slide 6: Lessons
So, what lessons can we learn from these two case studies in genome editing policy? Well, the first is that policies are collective: They represent competing interests and are the result of the work of many. Second, policies are flexible: they can be amended to fit the circumstances of their specific times and places. Third, and finally, policies are historical. They change through time, are context-dependent, and influence one another. These things are as true for genome editing policies as they are for all science policies, including those that the federal administrations may prioritize in the years to come