Tom Bollyky joined us on the occasion of our 100th episode to reflect on President Biden’s six-point re-set of US pandemic policy, unveiled September 9, and to discuss what can be done to break the deadlock over determining the origin of SARS-CoV-2. President Biden’s patience has clearly run out, and the new approach, heavily reliant on mandates, will stir political blowback, litigation, and defiant disobedience which may slow progress versus accelerate momentum. It’s “not a happy day” when people will be “pushed into a corner.” It’s disappointing that the private sector did not earlier do far more. Our national narrative may however improve, as higher rates of hospitalization of children deflate the individual freedom argument. On the origins controversy, it is “utterly unsurprising” that the US intelligence review was inconclusive. The origin issue is indeed terribly important, at this historic “policy moment,” since without resolution, we are blocked in our prevention approaches. We are in a “dark environment” and there is no prospect for progress in global health unless we find a basis for cooperation between the US and China. In the meantime, we should prioritize moving ahead with more rigorous lab safety standards and end wildlife trade and wet markets. Thomas J. Bollyky is the Director of the Global Health Program and Senior Fellow for Global Health, Economics, and Development at the Council on Foreign Relations.