Biostasis (aka cryonics) is a field that is slowly revealing its possibilities to the world. Scientific, technological and medical research are advancing at an incredible pace, allowing us to achieve things we would have never believed possible. What are the latest findings on cryopreservation? How far are we from creating banks of cryopreserved organs? What stops us from successfully reviving a human being? To answer some of these questions, we decided to interview Roman Bauer, renowned scientist working on Computational Biology.
Roman Bauer - neuroscience, AI, cancer research and cryopreservation
You may wonder: what exactly does a computational biologist do? The term covers a range of jobs, from data analyst, data curator, database developer, statistician, mathematical modeler, bioinformatician, software developer… Basically all those scientists that decided to rely on new technologies for the development of analyzed data and useful models.
Roman Bauer is a good example of an interdisciplinary scientist. After a Master’s Degree in Computational Science and Engineering with Specialization in Theoretical Physics and Robotics, Bauer earned a Ph.D. in Computational Neuroscience at the Institute of Neuroinformatics in Zurich. One of the various projects for which he is famous is a free accessible software, the BioDynaMo platform created in 2015 in collaboration with the University of Surrey, CERN and multiple other institutions. This platform allows computer science experts and non-experts to create, run, and visualize 3D agent-based biological simulations.
Together with his interest in computational neuroscience, machine learning and AI, and cancer research, Bauer has spent some time working on mathematical and computational tools to optimize cryopreservation protocols. And it is on the basis of this knowledge that we decided to ask him a few questions!
How and when did you get interested in cryopreservation?
It was about 10 years ago, during a time when I started thinking more deeply about mortality. It was mainly due to the death of a very good friend of mine. He was diagnosed with cancer at the age of 32, and died 2 years later. His cancer and subsequent death happened despite his very healthy lifestyle (he had never smoked, never drank alcohol, did competitive sports, etc.). I experienced his feelings and the impact that his condition had on his family and friends. This event really woke me up and I thought how wonderful it would be if there were a way to pause the dying process that entails so much physical as well as mental pain.
My interest in the underlying science of cryopreservation followed from there, initially on a purely curiosity-driven basis. It was during my postdoctoral time that I truly grasped the potential of my computational methods for biomedical applications, and also started working on the topic of cancer. I understood that my methods could be applied to various topics including cryopreservation.
How is cryopreservation currently used? And how could it be used in the future?
Currently, cryopreservation is predominantly being used for the preservation of cells (e.g., sperm, stem cells, seeds) rather than tissues. Moreover, it is mainly based on experimental techniques rather than computational methods. So there is a lot of heuristic work and trial-and-error based work. There is also a gap between what can be achieved for cells and organs/individuals today, and I find it very exciting to work on closing this chasm.
What are the challenges connected with cryopreservation and why is it so hard to achieve thawing on more complex tissues?
The nature of the challenges depends on the cryopreservation process. There are two well-established methods, namely “vitrification” and “slow-cooling”. Vitrification has led to many advances and is currently more widely used than slow-cooling. However, it requires that the temperature drops quickly, which is not an option for volumes at the scale of organs. Otherwise very high concentrations of toxic cryoprotective agents are required. Hence, such toxicity is highly problematic for complex tissues.
There is a very promising opportunity here for studying novel chemicals that are less toxic. In fact, some animals produce antifreeze substances that allow them to survive very low temperatures. Taking inspiration from natural phenomena is a very exciting research direction.
On the other hand, slow-cooling does not require quick temperature drops. It is therefore more easily scalable in terms of tissue volume. However, the problem with slow-cooling is the formation of ice crystals in extracellular space. There exist ways to reduce or even avoid such ice formation, but more research is needed to obtain better results. It is astonishing that, while water is so common in the world, it is yet so complicated!
How is AI and machine learning helping us solve these challenges?
The usage of computational modeling and simulations in cryopreservation is growing, as there is significant potential. Indeed, computational/bioinformatics methods have already revolutionized so many other biomedical fields such as genomics or neuroscience. In my recent research project funded by the Engineering and Physical Sciences Research Council of the UK (EPSRC), we exactly address this opportunity. We are currently in the process of writing up our results, which confirm that there is a lot to be gained from applying ML techniques. Along those lines, we can create a “virtual testbed” to computationally simulate expected changes to cells, and use sophisticated optimisation methods to determine better protocol parameters. I am describing this work also on my personal website www.romanbauer.net.
In your opinion and knowledge, how far are we from finally succeeding?
If by “succeeding” you mean the capability to cryopreserve human organs: this is very difficult to say because science does not progress predictably. Einstein famously said: “If we knew what it is we were doing, it would not be called research. Would it?”. But I know that we are currently only scratching the surface, and the field needs to gain momentum. I don’t know of any University programme where there is a dedicated module on cryopreservation. Instead, cryopreservation is more often understood as a set of protocols that are employed on demand, as a service to research groups. If there was more appreciation for cryopreservation as an academic field of research and topic for student education, it would go a long way.
Speaking of human cryopreservation, when and how did you meet this topic for the first time?
I suppose it was a story or movie (probably the classic fairy tale “Dornroeschen” or maybe the movie “Forever Young” with Mel Gibson) when I first came in touch with this idea of preserving a human. At the time, I was very young and did not think much more about it. But it sort of lingered at the back of my mind, and galvanized when I read “The Prospect of Immortality” by Robert Ettinger.
What are the consequences connected with the success of thawing and revival?
It would be the biggest achievement of humanity since the invention of the wheel. Patients with terminal cancer or severe degenerative diseases would have the chance to be cured in the future. Long-distance space travel and the colonization of outer planets would become viable options. Emergency medicine would be revolutionized. The positive consequences are numerous.
How could organ and human cryopreservation improve our society?
Both types of cryopreservation would be of immense value. The study of Giwa et al. (Nature Biotechnology, 2017) claims that the availability of sufficient organs could theoretically prevent > 30% of all deaths. The healthy lifespan of the average human would be significantly improved.
I think human cryopreservation would also improve society because it would promote long-term thinking. The knowledge that our lives can realistically be much longer than 80 or 90 years would entail more considerations and motivation for living together as a flourishing society, as well as on a healthy planet.
Biostasis and organ banks could be great tools towards equality. But how do we make sure we go in the right direction?
Cryopreservation is currently less academic and receives less public funding than many other scientific fields. I noticed that particularly well because my background is in Computational Neuroscience, where there is a long-standing and well-established culture of freely available datasets and tools. Commercial interests and legal restrictions play a big role in cryopreservation, which has led to lots of IP being protected or licensed, and rendering it more challenging to easily collaborate and democratize the research. So I think we need more research funding where it is a requirement for the results to be made available as open access, and that supports international collaboration.
It is because of such reasons that I myself co-founded the BioDynaMo collaboration, where we created an open-source software to model biological systems, including the cryopreservation of cells and tissues. We are now a collaboration of 9 institutions from 6 different countries, and we are strongly committed to making our results, resources and skills accessible to the research community. We hold regular meetings where everyone who is interested can join. It would be great if we could collaborate more with cryopreservation researchers and create a platform where data and protocols are shared.
If you could make people reflect about something, what would it be?
Cryopreservation is a young and small field that has lots of potential. You don’t need to be a researcher or a billionaire to contribute to it, nor do you need to be involved full-time. If you are willing to commit, there is a way to make a big difference. So if you are interested in this topic, my advice is to think very carefully about what path fits best with your mindset, your passions and what really energizes you.
Roman Bauer at Biostasis2021
At the Biostasis2021 Conference, we had the pleasure to personally meet Roman Bauer and listen to his talk about "The Future of Cryopreservation: Computational Approaches and Automatisation". Check the full speech if you want to learn more about his project BioDynaMo and about his effort in building a computational approach to cryopreservation.
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