Case Three: The Magic Key

RCR Casebook: Social Responsibility

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Sarah is a talented postdoctoral fellow working in a biosafety facility on modes of cellular entry of the herpes viruses through the interaction between glycoproteins in the envelope of the virus and cell surface receptors. She has performed scanning mutagenesis of an envelope protein as part of a standard structure function project. Sarah is under the gun to get the mutants screened, so she is testing her constructs for viral entry before she even gets their sequences confirmed. One of the mutations has a startling phenotype: it is 100 times more infectious. One of the oligonucleotides Sarah ordered for her mutagenesis must have been synthesized incorrectly, because after getting the sequence back Sarah realizes that it is nothing like what she had ordered. What a lucky coincidence!

Sarah is very curious about how the mutated sequence facilitates viral entry. Just for kicks, she uses the mysterious oligo on another envelope virus she is studying, and it has the very same effect! Now she is really starting to get excited! Could it be that she has fortuitously discovered some type of a master key that allows viruses’ easy access into cells? So many of their experimental challenges have to do with getting viruses into cells efficiently; her work could be a critical breakthrough! She is preparing for her upcoming lab meeting presentation, and has now tried the sequence on six different viruses. They all have worked beautifully. Sarah cannot help but also think about how this discovery could impact her own career. She thinks this is a Science or Nature paper, for sure. This paper would likely mean a world of difference for her upcoming job search for Assistant Professor positions. Sarah believes that her mentor would allow her to propose follow-up experiments for her own NIH R01 grant, too. Suddenly, her whole life seems to be transformed in wonderful ways!

The night before her lab meeting presentation, Sarah is a bit nervous. Although she has mentioned the experimental results in passing to her mentor, the full impact of her finding has clearly not hit him yet. She wants to really impress him with how well she has performed the critical experiments and the controls. She goes over her presentation again and again. Finally, she arrives at the point in the presentation where she discusses the "implications" of her work. Well, it means that virtually any virus can be studied, and any virus can be made to be highly infectious. Sarah blanches. Her discovery could have “dual use” potential—that is, in the wrong hands her findings could be used to develop bioweapons! How could she have been so blind? Her advisor might not only not be enthusiastic, he might not allow her to publish her findings! Sarah realizes that the Institutional Biosafety Committee might have concerns, too; she did not have approval to pursue this line of inquiry, it just arose from the bad oligo. Would they make her discontinue her experiments? Would they block her publication? Could she actually be in some kind of trouble?

What should Sarah do?

Discussion Questions for the Facilitator

  • Why do you think Sarah believes her research might have a “dual use of concern”? Do you think she is correct?
  • Should scientists be able to work and publish freely on research that could be weaponized or used for terrorism?*
  • It is always possible to predict how others might use research for harm rather than good?
  • How do you think members of the Institutional Biosafety Committee would respond if Sarah contacted them, told them what had happened, and asked for approval to continue with this research?
  • Do you think Sarah has done anything wrong in this scenario?

Source URL: https://ori.hhs.gov/case-three-magic-key