Development of an N-1 perfusion process and optimized scale-down models for implementation in a platform CHO cell culture manufacturing process

The use of N-1 perfusion, coupled with high-inoculum fed batch in CHO cell culture manufacturing processes, has been shown to increase volumetric productivity and shorten the duration of the fed-batch production phase. Implementation of N-1 perfusion as part of a platform process requires the ability to screen multiple clones and to optimize media and process parameters in a high-throughput manner. We have developed an N-1 perfusion process, along with a series of scale-down models for N-1 perfusion using shake flasks, cell culture tubes, and deep-well plates. Process parameters for scale-down models were optimized to maximize comparability of growth profiles and cell culture performance relative to 5L N-1 perfusion bioreactors. Scale-down models were used to inoculate fed-batch experiments in Ambr15 micro-bioreactors at high seeding density, in order to compare growth and productivity profiles to those observed in 5L bench scale bioreactors. Multiple cell lines derived from different CHO hosts were evaluated in order to verify the robustness of the scale-down models. Results demonstrated that cell growth and viability in the optimized scale-down models were comparable to those observed in 5L N-1 perfusion bioreactors. Furthermore, growth, productivity, and product quality profiles from high-inoculum fed-batch experiments were comparable regardless of inoculum source. Optimized scale down models of N-1 perfusion, coupled with Ambr15 fed-batch production micro-bioreactors, have now been integrated into a high-throughput and robust workflow to enable DOE and screening experiments for clone selection, media development and parameter optimization in a platform N-1 perfusion process for monoclonal antibody manufacturing

Reply to Ellis et al.: human niche construction and evolutionary theory

We are pleased Ellis et al. found value in our recent synthesis of the deep history of human impacts on global ecosystems and agree that our paper should influence the current debate on if and how an Anthropocene epoch is defined. We also agree that the ecological consequences of human niche construction have profound and growing effects on the evolutionary trajectories of humans and other species living within human-altered ecosystems. Niche construction theory (NCT) provides an explicit framework for linking evolutionary and ecological processes into a coherent theory of biological evolution. Of special appeal to us as archaeologists is that NCT bridges biological and cultural evolution by including human culture and social learning within the mechanisms of evolutionary change, allowing scientists to address issues at the interface of human and natural systems. Some of us have contributed significantly to human NCT, addressing some of the very issues raised by Ellis et al. Finally, we agree that human transformations of ecosystems are inherently social processes—clearly humans are intensely social organisms—and that such processes result from long-term melding of biological and cultural evolution

Reply to Westaway and Lyman: emus, dingoes, and archaeology’s role in conservation biology

In a curious comment on our PNAS Perspective, Westaway and Lyman offer two Australian zooarchaeological case studies—one involving eggshells and the other dingoes—that they argue undercut one of our main points: that archaeological data and deep time perspectives have much to offer conservation biology. Neither example provides a specific substantive critique of our perspective: there are no dingoes in our article, no eggshells, and we mention the long and rich record of human management and alteration of Australian environments only briefly. Nor do we suggest that all archaeological assemblages can effectively inform current conservation biology efforts. Such datasets obviously vary in their quality and potential applicability to modern situations. When considered more closely, both of Westaway and Lyman’s case studies underscore rather than undercut the importance of archaeological and paleoecological data in conservation biology initiatives

An Anthropocene Without Archaeology—Should We Care?

For more than a decade, a movement has been gathering steam among geoscientists to designate an Anthropocene Epoch and formally recognize that we have entered a new geological age in which Earth’s systems are dominated by humans. Chemists, climatologists, and other scientists have entered the discussion, and there is a growing consensus that we are living in the Anthropocene. Nobel Prize-winning atmospheric chemist Paul Crutzen (2002a, 2002b; Crutzen and Stoermer 2000) coined the term, but the idea that humans are a driver of our planet’s climate and ecosystems has much deeper roots. Italian geologist Antonio Stoppani wrote of the “anthropozoic era” in 1873 (Crutzen 2002a), and many others have proposed similar ideas, including journalist Andrew Revkin’s (1992) reference to the “Anthrocene” and Vitousek and colleagues (1997) article about human domination of earth’s ecosystems. It was not until Crutzen (2002a, 2002b) proposed that the Anthropocene began with increased atmospheric carbon levels caused by the Industrial Revolution in the late eighteenth century (including the invention of the steam engine in A.D. 1784), however, that the concept began to gain serious traction among scientists and inspire debate

Disease drivers of aging.

It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging

Disease drivers of aging.

It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging