study mpox, even when it was not an epidemic infection, in order to generate the kind of information that we have today. That information serves as the foundation for the development of a whole variety of strategies, including the vaccine that is now used to prevent mpox (Jynneos). Dr. Moss’s critical insight was to recognize that the different strains or clades of mpox had different levels of virulence. Clade I was very virulent, while clade II was not. Therefore, since only about 5% of the DNA differed between these two strains, there must be specific DNA differences that determined why one strain was highly virulent and fatal in up to 10% and the other less so. These molecular changes are critical to identify if we are going to understand viral pathophysiology and human disease. Dr. Moss’s innovation, using the molecular tools his laboratory developed, the building infrastructure and the extensive safety support of the NIH, was to replace specific genes of the more virulent clade I with genes from the less virulent clade IIa to see if he could diminish the virulence of the more severe virus in a rodent model. This is the most cautious approach, trying to attenuate the virulent strain, and this was the approach that Dr. Moss has taken. He has not at any point pursued transferring genes from the more virulent strain (clade I) into the less virulent strain (clade II), nor has he made specific plans to do so. If the latter strategy were to be pursued in the future, it would be preceded extensive consultation and rigorous evaluation and review by the committees that Jeff Potts will discuss shortly, which exist to ensure in-depth safety assessments.
Let me speak for a moment about the imperative of performing this kind of research. It remains a deep concern to all of us thinking about pandemic preparedness that we may be only a plane flight away from transmission of a more virulent strain of mpox, clade I. The fact that the epidemic strain of 2022 was from the less virulent clade II is a wake up call that we need higher vigilance and much more research in order to identify and create appropriate countermeasures. In fact, it was Dr. Moss’s work in particular that proved that Jynneos was effective against mpox in nonhuman primates, which indicated that this would likely be successful for preventing mpox in humans.
I genuinely appreciate and share the concern of this committee, as do my colleagues, to understand, anticipate and prevent pandemic disease. We are all in agreement that viral infections are a concern for the entire human family. I believe we are also in agreement that it is only through careful, insightful scientific research that we will be able to anticipate, understand, prevent, and treat these deadly diseases.
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