Transdisciplinary pragmatic melioration for the plastic life cycle: Why the social, natural, and technical sciences should prioritize reducing harm.

Plastics underpin modern society but also threaten to choke it. Only 9 % of all plastic waste is recycled, usually with loss of quality ("downcycling"); the rest is landfilled or dumped (79 %) or incinerated (12 %). Put bluntly, the "plastic age" needs a "sustainable plastic culture." Consequently, we urgently need to develop a global and transdisciplinary approach not only to fully recycle plastics but also to manage the harms across their life cycle. The past decade has witnessed an explosion in research on new technologies and interventions that purport to help solve the plastic waste challenge; however, this work has, in most cases, been carried forward within single disciplines (for example, researching novel chemical and bio-based technologies for plastic degradation, engineering processing equipment innovations, and mapping recycling behaviours). In particular, although there has been vast progress within individual scientific fields, such work does not address the complexities of various plastic types and waste management systems. Meanwhile, research on the social contexts (and constraints) of plastic use and disposal is rarely in conversation with the sciences to drive innovation. In short, research on plastics typically lacks a transdisciplinary perspective. In this review, we urge the adoption of a transdisciplinary approach that focuses on pragmatic melioration; such an approach combines the natural and technical sciences with the social sciences to focus on the mitigation of harms across the plastic life cycle. To illustrate our case, we review the status of plastic recycling from these three scientific perspectives. Based on this, we advocate 1) foundational studies to identify sources of harm and 2) global/local interventions aimed at those plastics and aspects of the plastic life cycle that cause maximal harm, both in terms of planetary welfare and social justice. We believe this approach to plastic stewardship can be a showcase for tackling other environmental challenges.

In vitro and in silico assessment of the developability of a designed monoclonal antibody library.

Despite major advances in antibody discovery technologies, the successful development of monoclonal antibodies (mAbs) into effective therapeutic and diagnostic agents can often be impeded by developability liabilities, such as poor expression, low solubility, high viscosity and aggregation. Therefore, strategies to predict at the early phases of antibody development the risk of late-stage failure of antibody candidates are highly valuable. In this work, we employ the in silico solubility predictor CamSol to design a library of 17 variants of a humanized mAb predicted to span a broad range of solubility values, and we examine their developability potential with a battery of commonly used in vitro and in silico assays. Our results demonstrate the ability of CamSol to rationally enhance mAb developability, and provide a quantitative comparison of in vitro developability measurements with each other and with more resource-intensive solubility measurements, as well as with in silico predictors that offer a potentially faster and cheaper alternative. We observed a strong correlation between predicted and experimentally determined solubility values, as well as with measurements obtained using a panel of in vitro developability assays that probe non-specific interactions. These results indicate that computational methods have the potential to reduce or eliminate the need of carrying out laborious in vitro quality controls for large numbers of lead candidates. Overall, our study provides support to the emerging view that the implementation of in silico tools in antibody discovery campaigns can ensure rapid and early selection of antibodies with optimal developability potential.