Ambitious project aimed at stopping biological time advances science ahead of schedule
By Lindsay Brownell
(BOSTON) — The Wyss Institute’s Biostasis project, which began just eighteen months ago as part of the Defense Advanced Research Projects Agency (DARPA)’s Biostasis program, has successfully completed its project Phase 1 goals and moved into Phase 2 this month, on schedule despite the disruption of the global COVID-19 pandemic. This ambitious project aims to identify biostasis inducers – molecular compounds that can reversibly slow or even stop the processes of cellular metabolism at room temperature – which could be used to stabilize vaccines without the need for a cold chain of transportation, preserve cellular therapies and organs for transplantation, and buy time to treat people with life-threatening injuries.
“I am very proud of this team and what we have been able to accomplish in such a short period of time – to go from a ‘moonshot’ idea on paper to a multidisciplinary research effort that is moving into in vivo experiments so quickly is just breathtaking,” said Isabel Chico-Calero, Ph.D., D.V.M., the Biostasis Project Manager at the Wyss Institute. “We made so much progress that we were even able to seamlessly begin some Phase 2 activities before Phase 1 was over.”
The Biostasis project involves team members from multiple labs, platforms, and disciplines across the Wyss Institute community. In order to identify compounds that could potentially induce biostasis, the group designed, built, and is using a development pipeline to find candidate substances, analyze them for traits that indicate biostasis-related activity, and evaluate them using computational methods. Simultaneously, candidate compounds are tested experimentally and those results are fed back into the pipeline, refining it over time to make its predictions more accurate.
“I’m completely blown away by the coherence and energy of the team – everyone is working together really well, addressing the challenge from different perspectives. We’ve already gotten some really interesting insights into the timing and regulation of biological processes, and it will be fascinating to see it transitioned into practical applications in Phase 2,” said Michael Levin, Ph.D., an Associate Faculty Member of the Wyss Institute, and the Vannevar Bush Chair Professor and Director of the Allen Center for Discovery at Tufts University, whose lab is working on multiple experimental aspects of the Biostasis project.
The foundations of the Biostasis project have also been deployed in the worldwide fight against COVID-19. Three computational pipelines that were being pursued as part of the Biostasis project are now being used to predict and identify existing drugs that could have effects against the CoV-2 virus as part of a new DARPA program. The first promising compounds are being tested in Organ Chip and animal models by collaborators at the University of Maryland Medical School and the Icahn School of Medicine at Mount Sinai, and the team is in close contact with other government agencies regarding moving any effective compounds into clinical trials.
“This project underscores the importance of having a multidisciplinary team that’s comfortable taking scientific risks in solving difficult problems like inducing biostasis. Our group has become a self-driving engine of innovation, even beyond the problem at hand, and I’m grateful to be part of the team,” said Richard Novak, Ph.D., a Senior Staff Engineer on the Advanced Technology Team and co-lead of the Biostasis project.
In Phase 2, which will last twelve months, the Biostasis team will continue to refine their pipeline based on experimental data. They are also testing compounds in human Organ Chips, and are integrating metabolic sensors into the chips to further evaluate how the compounds affect organ systems. Their lead compounds are being tested in collaboration with Lackland Air Force Base in San Antonio, Texas, where they are being evaluated for their ability to affect metabolic processes in whole vascularized tissues during organ transplantation in a large animal model. This work, if successful, could lay the groundwork for a new method of preserving human organs and limbs for transport to people who need them, and also brings the Biostasis project one step closer to fruition.
“When we wrote the grant application and laid out a plan for developing biostasis therapeutics that could effectively induce a state of suspended animation, it truly read like a science fiction short story. But turning that fiction into reality is what the Wyss Institute is all about, and the progress we have made in such a short time is amazing. I am incredibly proud of the team who are working together so well to make this happen,” said Donald Ingber, M.D., Ph.D., who is leading the Biostasis project with Novak. Ingber is the Wyss Institute’s Founding Director, as well as the the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).