In Episode 20, we continue with our theme of the planetary boundaries (PB), turning to perhaps the most perplexing of them: so-called ‘novel entities’, or the release of things that are ‘new’ into the environment, including chemical pollution, but also new life-forms, pharmaceuticals, radioactivity or nano-particles. As the notorious case of CFCs and the Ozone layer has shown (eliciting a planetary boundary all of its own!), the mass release and accumulation of such novel entities can have negative, and potentially irreversible, global impacts that take us entirely by surprise. Yet we continue the relentless development and release of ever more, and ever more complex, chemicals and technological entities. It is thus little surprise that the latest assessment of the planetary boundaries (as discussed in Episode 19) concludes that we are well outside the ‘guardrail’ for this issue. But the current state of play is, arguably, the least of our worries. More troubling is a seemingly inescapable conundrum regarding the very epistemic predicament to which the novel entities PB awakens us: namely that this is problem of fundamental ignorance and with the highest of stakes. To unpack this crucial and unprecedented challenge for science and environmental policy, we are delighted to be joined by two of the key scientists who have identified, formulated and explored this challenge and what we can do about it: Professors Cynthia De Wit and Matthew MacLeod. Across a wide-ranging discussion, we go into the challenges of doing science on issues characterised, by definition, by irreducible ignorance; the key issue of time, and hence the parallel challenges of rate of release and rate of (effective regulatory) understanding; how the ‘novel entities’ PB reframes and reinforces the precautionary principle; and much more…