INTRODUCTION: The Ethical, Legal & Policy Challenges of Stopping Biological Time

Human beings depend on biological materials for survival — everything from food to medical interventions such as organ transplantation, to the environments in which we live. So it is no surprise that techniques to avoid the deterioration of biological materials have been used since ancient times.¹ Cooling is one of the oldest techniques. Indeed, most of us now live with a cooling machine — a refrigerator — in our kitchens. But the function of those machines is primarily to retard the spoilage of materials that are already in the process of disintegrating: fruit that has already been harvested, meat from beef and chickens already slaughtered, and milk already derived from cows.

Beginning in the mid-20th century, scientists began to develop techniques for cryopreservation with more ambitious goals in mind. Instead of merely slowing the deterioration of biological materials, techniques could be developed to preserve living materials for prolonged periods of time and then allow their revival and use at a future time and place. An early application was cryopreservation of sperm (both human and animal), allowing sperm banking and later use.² Yet conventional cryopreservation had its limits. Prolonged preservation of solid organs for transplantation was among the applications that proved elusive.

Nature offered intriguing models, though, suggesting that prolonged preservation of biological materials followed by return to full function was possible. Both the Arctic ground squirrel and wood frog regularly undergo suspended animation to survive their frozen environment, followed by return to full function.³ Understanding how these organisms survive extreme temperatures opened new avenues for exploration.

The 21st century is now seeing an explosion of interest in new techniques for biopreservation.⁴ These techniques manipulate temperature, cryoprotective agents, infusion of nanoparticles to allow uniform rewarming, and the containers used in order to successfully control the entire process of cooling, storage, and rewarming to full function. Supercooling, partial freezing, vitrification, and nanowarming are among the techniques showing remarkable promise in a range of biological materials, from cells to tissues, whole organs, and even whole organisms.⁵

In 2020 the National Science Foundation (NSF) awarded major funding to create the Engineering Research Center (ERC) for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio).⁶ The ERC program began nearly 40 years ago and has funded scores of ERCs to conduct convergent and revolutionary research.⁷ The ATP-Bio ERC crosses six core research institutions: the University of Minnesota (UMN), Massachusetts General Hospital (MGH), University of California Berkeley, University of California Riverside, Texas A&M University, and Carnegie Mellon University. Led by John Bischof, Ph.D. (UMN) and Mehmet Toner, Ph.D. (MGH), ATP-Bio is working to enable advanced biopreservation at multiple scales (from cells and tissues to whole organs and organisms). These flexible, enabling technologies will have a wide range of uses across three major spheres: biomedicine, food systems, and environmental conservation.

This symposium grows out of EPP’s efforts to map the landscape of ethical, legal, and policy challenges posed by the advanced biopreservation techniques that ATP-Bio scientists are developing. Analyzing these challenges has proven demanding. Advanced biopreservation is an evolving suite of techniques with an enormous range of potential applications spanning health, food, and environmental conservation. Anticipating impacts in these spheres is a predictive exercise with associated uncertainties. The one certainty is that the challenges will be profound.

In funding ATP-Bio, NSF built a novel structure. For the first time, the agency embraced the need to ensure ethical, legal, and societal analysis of the revolutionary technology under development. ATP-Bio thus has a dedicated Ethics & Public Policy (EPP) component, directed by Susan M. Wolf, J.D., and co-led by Timothy Pruett, M.D.⁸ Though some past ERCs had examined ethics, ATP-Bio is the first to our knowledge to build a dedicated component into the center’s structure, though some other ERCs now have similar units. This reflects NSF’s evolving ambitions for the ERC program, from the goal of successful translation and commercialization to the larger goal of achieving net societal benefit. In addition to ATP-Bio, NSF now funds other ERCs with dedicated attention to societal impact and community engagement. Indeed, NSF has now convened a Stakeholder Engagement & Impact Collaborative (SEIC) across the current ERCs to share methods and insights.⁹

The EPP component in ATP-Bio depends on the expert contributions of a 13-member Ethics & Public Policy Panel (EP3) ( Table 1 ). From the start of our EPP work, this team has used multiple methods to analyze the ethical, legal, and societal implications of ATP-Bio research and technology development. These have included literature analysis; consultation with science, engineering, and biomedical experts inside the ERC and beyond; and consideration of multiple techniques for assessing the implications of emerging technologies. Those techniques include but are not limited to responsible innovation, anticipatory governance, horizon scanning, and a range of techniques associated with the National Institutes of Health’s (NIH) ELSI program.¹⁰ Helpful models have included those utilized by relevant study committees at the National Academies of Sciences, Engineering, and Medicine.¹¹

Table 1

This symposium grows out of EPP’s efforts to map the landscape of ethical, legal, and policy challenges posed by the advanced biopreservation techniques that ATP-Bio scientists are developing. Analyzing these challenges has proven demanding. Advanced biopreservation is an evolving suite of techniques with an enormous range of potential applications spanning health, food, and environmental conservation. Anticipating impacts in these spheres is a predictive exercise with associated uncertainties. The one certainty is that the challenges will be profound. Advanced biopreservation —including vitrification — has the potential to suspend biological time. Cells, tissues, organs, and even whole organisms can be placed in a kind of suspended animation for an indefinite period of time, to be reanimated in a distant future and place. This has the potential to alter fundamentally the familiar rules governing biological life — life and then death in predictable geographical spaces. Advanced biopreservation may enable indefinite organ banking for transplantation, aquaculture to bring protein to more of the world, preservation of endangered species and transport to new environments, and even prolonged space travel.

The articles in this symposium tackle all of those potential applications and more. In Section 1 of the symposium, four articles map the challenges of advanced biopreservation. The first article by Wolf et al. on “Anticipating Biopreservation Technologies that Pause Biological Time: Building Governance & Coordination Across Applications” canvasses the challenges across the major domains of potential application to analyze what governance innovations are needed and how to coordinate governance across disparate regulatory and oversight regimes. The second article by Maynard et al. on “Successfully Bridging Innovation and Application: Exploring the Utility of a Risk Innovation Approach in the NSF Engineering Research Center for Advanced Biopreservation Technologies (ATP-Bio)” reports the results of a novel workshop process inviting ATP-Bio Partners — the commercial, nonprofit, and government entities already engaged with the ERC — to systematically identify perceived areas of value and threats in translating advanced biopreservation methods to application. The third article by Childress et al. on “Ethical Issues in Emerging Technologies to Extend the Viability of Biological Materials Across Time and Space” applies an overarching ethical framework to consider the challenges posed in advanced biopreservation in three domains: organ and tissue transplantation and medical applications, food production, and environmental conservation. The fourth article by Hyun et al. on “The Need for Early Engagement with Interested Groups on Advanced Biopreservation” shows the importance of early engagement with all interested parties to guide development of this disruptive technology.

Section 2 then presents three articles focusing on biomedical applications. In “The Big Chill: Opportunities for, and Challenges to, Advanced Biopreservation of Organs for Transplantation,” Capron et al. examine challenges looming even at this early preclinical stage and argue for broad dialogue to set the stage for later development of regulation and oversight processes. In “An ‘Amazon of Living Things’? The History & Horror of Commodifying Life,” Goodwin urges the importance of evaluating efforts to biopreserve, store, and potentially commercialize body parts, cells, and tissues in light of the history of human commodification both in the United States and globally. Then in “Biopreserving Pathogens: Promise & Peril,” Jaskiewicz et al. consider the risks and benefits of biopreserving two important pathogens — Cryptosporidium and Plasmodium — the first of which is classified by the Centers for Disease Control and Prevention (CDC) as a Category B Bioterrorism Agent.¹²

Section 3 collects articles on applications in conservation biology and the food supply. In “Manipulating Time by Cryopreservation: Designing an Environmental Future by Maintaining a Portal to the Past,” Brister et al. consider how the use of advanced biopreservation is framed in environmental conservation, including metaphors of “stopping” or “freezing” biological time. Feys et al. then analyze the potential development and use of suspended animation to allow deep space exploration in “Biopreservation Beyond the Biosphere: Exploring the Ethical, Legal & Social Implications of Suspended Animation in Space.” Finally, in “Biopreservation in Agriculture and Food Systems: A Summary of Ethical Issues,” Thompson et al. use ethical analysis to examine the application of advanced biopreservation in both agriculture and aquaculture.

This symposium is the first to map the ethical, legal, and societal challenges posed by emerging biopreservation technologies across the wide range of applications envisioned. The authors are drawn from across ATP-Bio, including EP3‘s experts in ethics and emerging technologies, the ERC’s engineers and biomedical researchers, and additional colleagues with relevant expertise. Using multiple methods and disciplinary perspectives, we demonstrate the need for this kind of anticipatory analysis to inform research, development, oversight, and application. By embracing an examination of ethics and public policy as an intrinsic part of technology development and translation, ATP-Bio strives to integrate EPP considerations into ERC research, decisions, and progress.