October 7, 2022

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One Enabling Technology That Will Help Build The New Industry Of The Future

24 min read

Since the dawn of human civilization, people have been using the cold for the preservation of food. Early humans carved and stored ice next to food to keep it from spoiling. The use of low temperatures in medicine can also be traced back to medical procedures from ancient Egypt that were performed almost 5000 years ago. Even Hippocrates himself recommended the use of ice to stop bleeding and swelling. Nowadays, we know how to efficiently utilize the cold in many ways, from modern refrigeration to operating halls. Cold is used in modern surgeries, in vitro fertilization, and organ transplantation. But what else can cold do?

Apparently, the cold could keep our organs, our animals, and, hypothetically, even humans (one day), alive forever. Low temperatures slow down or completely prevent biochemical reactions from happening. No biochemical reactions – no development of diseases, no ticking aging clocks, no decay?

Imagine a world, where freezing and thawing of biological organisms without damage is available. In that world, if I had a terminal disease, I could freeze (or cryopreserve) myself before my body collapses and “wait“ until humanity discovers a cure for it in the future or “live” the remaining life freezing and unfreezing to “see” a bit more life and human progress. It does seem almost impossible today. However, cryobiology is not standing still. Cryopreserved human oocytes, sperm, and fertilized embryos have been used for years in successful in vitro fertilization births. Scientists have been experimenting with frozen and rewarmed cell cultures for years, and even used frozen skin grafts on burn victims. But for now, that’s about it. Living organs are still being transported very quickly using hypothermic temperatures, but they cannot be frozen and stored. Why can’t we freeze and rewarm the human body? The answers are a little more complicated than just the idea of immortality.

The problem in using cold is ice crystal formation, particularly from water which is a majority of mass in living systems. If the process of cooling and rewarming isn’t optimized to the fullest, ice crystals will form and the organism is going to go through something similar to “freezer burn“. Ice can cause tissue and organ damage from rapidly bursting cells. Tackling the “ice problem“ is a matter of integrating chemistry, biology, physics, and engineering into something that we now know as cryobiology. Every step of the way to immortality by cryopreservation requires extensive research and years of experimental work.

Thankfully, we already have people working on it. I was lucky to meet and interview the leading scientists in the field of cryobiology today, Prof. Dayong Gao at the University of Washington’s Center for Cryo-Biomedical Engineering and Artificial Organs in Seattle, and two of his group members, Dr. Shen Ren and Dr. Zhiquan (Andy) Shu.

The History of Cryobiology, Cryonics, and Cryogenics

Cryobiology is a subfield of science that studies the effects of low temperatures on living creatures, whereas cryonics is the act of cryopreservation with the intent of eventual reanimation. On the other side, cryogenics is a branch of physics and engineering that studies the production and technical use of very low temperatures. These terms can get confusing, so it’s important to know the differences between them.

None of mammalian cells can be cryopreserved until 1949 when English scientists, Christopher Polge, et al., accidentally discovered glycerol as a cryoprotective agent (CPA) for cryopreservation. In 1954, using glycerol, human sperm was frozen, rewarmed, and successfully used to impregnate three women. In 1959, Lovelock and Bishop discovered and characterized another CPA, dimethyl sulfoxide. CPAs react to water molecules and prevent them from forming harmful large intracellular ice crystals and the severe cell dehydration.

Some cell suspensions and thin tissue samples can be frozen and stored now, but freezing human cells for the purpose of reproduction is not the only current use of low temperatures in medicine. Since 1988, when the Organ Procurement and Transplant Network started recording the information on organ transplant surgeries, there have been more than 800 000 successful transplants and lives saved in the United States only. Without the storage of organs, even just for several hours, such procedures wouldn’t be possible. Currently, human organs can not be cryopreserved and can only be stored on ice (“hypothermic storage”) for a short period of time during transport from the donor to the recipient. Therefore, organs that cannot be transported on time will simply be lost due to irreparable tissue damage. If it would be possible to optimally freeze, store and thaw organs, the organ transplant waiting list could be cleared in several years, and more patients’ lives could be saved without the long waiting lists and burdening urgency.

There is also cryosurgery or cryoablation, which stands for intended tissue damage by ice formation, even though it’s not used as often. The first cryosurgery was performed in 1845 by James Arnott, the “father of modern cryosurgery“, when he used extremely low temperatures to freeze breast and uterine cancers. One more modern non-invasive cryosurgery is that damaged heart tissue or cells are treated and removed with cold liquids or probes. Clearly, the possibilities of using cold in medicine are endless.

The freezing of whole human bodies was proposed by the Michigan professor Robert Ettinger in 1962, in a book titled “The Prospect of Immortality“. The first frozen body, of a middle-aged woman from California, went through a real temperature rollercoaster. It was first embalmed for two months, then frozen in liquid nitrogen and then rewarmed and buried. There wasn’t much hope for future revival. The first human body was frozen with the intention of future revival in 1967 and it belonged to a psychologist James Bedford who died at the age of 73. That started the avalanche of new companies that offered the services of human cadaver cryopreservation. Six were established through the 70s, the golden era of cryonics. Unfortunately, it soon became too expensive for them to cryopreserve the growing number of bodies and keep them until the unpredicted future. Huge scientific advances in cryonics, like successful revival processes or curing of several diseases, simply did not happen as quickly as everybody hoped at the time. There are only a few companies in the world today that offer services of human body cryopreservation and storage.

In 1972, Austrian-born scientist and a huge name in cryobiology, Peter Mazur, published first-ever successful cryopreservation of mammalian embryos using slow-freezing with his colleagues Stanley Leibo and David Whittingham. In 1983, the first human embryo was successfully cryopreserved. Ever since then, cryopreservation of human blood, stem cells, sperm, oocytes, and embryos, with more than 300 000 births happening from frozen embryos today.

In the 1980s, scientists Gregory M. Fahy and William R. Fall introduced the process of vitrification to cryopreservation and claimed it doesn’t cause any damaging ice crystal formation. Much of this work was supported by Peter Mazur’s research. Vitrification stands for rapid cooling of liquid medium until it becomes glass, or a non-crystalline amorphous solid. Since water is a major part of biological solutions, CPAs need to be added before rapid cooling to prevent ice crystal formation. CPAs act like antifreeze and lower the freezing point of water, preventing its molecules from gathering together in crystals. Below -100˚C, water molecules are locked in place and the entire liquid is a glass-like solid. This is a well-established practice in in vitro fertilization, specifically when freezing eggs, but it can be used to freeze any biological materials, like tissues, organs, or whole organisms.

Nowadays, Gregory Fahy is the Vice President and Chief Scientific Officer at Twenty-First Century Medicine, a Californian research company, where he continued to do a lot of work on vitrification, mainly of organs. In 2005, he announced successful cryopreservation of a rabbit kidney that was rewarmed and transplanted into a rabbit that lived a long life supported by that one kidney alone.

What does the process of cryopreservation look like?

First of all, a subject would give his or her consent and be pronounced legally dead before any of the cryopreservation techniques would be conducted. In the next minute or two the mechanical restoration of breathing and blood circulation happens. Then the subject’s body would be cooled to low temperatures and vitrified. The company providing the service would ship the subject off as soon as possible to the cryonics facility. At such low temperatures, all biochemical reactions significantly slow down and my body doesn’t decay or suffer damage. For successful cryopreservation, blood would be replaced from my body by a specific cocktail of CPAs and it would be stored in liquid nitrogen at temperatures about -196˚C in a very futuristic-looking tank.

The process may sound pretty straight forward, but the following critical problems can occur along the way as revealed from fundamental cryobiology research (note: Cryobiologists and the Society for Cryobiology have focused on the basic and applied cryobiology, and have no connection with cryonics.).

· Cooling and vitrification – there are many methods to perform vitrification, from rapid cooling and drying using noble gasses to using various concentrations of CPAs. Each of these methods can cause ice crystal damage if not performed optimally.

· Choosing the right CPAs and the way to add and remove them – glycerol, dimethyl sulfoxide, and other CPAs can be toxic to living organisms in certain high concentrations and the formulation of CPAs cocktails needs to be optimized very carefully.

· Storage – if human bodies need to be stored for decades or even centuries without changes in the atmosphere or temperature, very safe and stable storage facilities need to be established.

· Rewarming – once the body is rewarmed, recrystallization of ice can happen and cause irreparable damage to the body. If the body cannot regain its vital functions after rewarming, the whole process of cryopreservation fails.

Signing up for Cryopreservation: The List of Available Options is not Long

Currently, there are only a few facilities in the world that offer the service of human cadaver cryopreservation. In the United States, those are Alcor Life Extension Foundation, founded in 1972 by Fred and Linda Chamberlain in Arizona, and the Cryonics Institute founded in 1976 in Michigan by Robert Ettinger, the so-called “father of cryonics“. The Cryonics Institute currently has 150 cryopreserved patients, while Alcor has more than 190. If I want to cryopreserve my body for the future, I would need to pay somewhere between US$28,000 at the Cryonics Institute and $200,000 in Alcor. Clearly, the procedure is costly and determined by all the necessary steps along the way.

There are several other cryonics organizations in the world. The notable organization that I visited personally during my visit to Jinan in Shandong province called Yinfeng Life Science Research Institute in China, founded as a division of the Yinfeng Biological Group in 2015. They cryopreserved their first patient in 2017.

Recently, a few smaller research start-ups popped up on the scene, such as X-Therma, a company dedicated to improving regenerative medicine by using low temperature based in Berkeley, California. Their research is directed toward studying nature’s evolutionary defenses against ice formation and using nanoscience to create new and improved CPAs used in cryopreservation. Another one is Arigos, founded in Santa Clara, California, by Tanya Jones as its Chief Operating Officer. Their main focus is developing the methodology for the long-term banking of organs for the transplant industry.

However, given the uncertainty on when exactly we can successfully reanimate cryopreserved humans, there isn’t much more commercial interest in the field. Currently, governmental restrictions on the act of cryonics don’t exactly exist, at least in the United States, Germany or Russia, the potential investment possibilities are endless. However, the projected time of the first possible human revival is projected to happen in 82 years , which is not tempting for the big-shot investors that want to see their money return quickly.

Cryobiology in Academia:

The situation in academic circles differs very much from industry. There are a number of academic groups conducting research on cryobiology and cryopreservation all over the world.

In the USA, one of the groups is led by Prof. Boris Rubinsky of the University of California at Berkeley. Their research is focused on heat and mass transfers in low-temperature biology, bio-electronics, and biomedical devices. University of Minnesota’s Institute for Engineering in Medicine and Surgery contains an Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio) led by John Bischof. They aim to “stop biological time“ and extend the ability to store and transport cells, tissue, organs, and whole organisms. Dr. Adam Higgins leads the biomedical process engineering group at the Oregon State University, which researches the stabilization of biomedical material by using cryopreservation, lyophilization, and spray drying. Dr. Kevin Brockbank’s group of the Medical University of South Carolina researches cell, tissue, and organ cryopreservation for test systems and transplantation.

In Canada, Dr. Jason Acker leads a cryobiology group at the University of Alberta in Edmonton. His group deals with the understanding of the biological response of cells to freezing and freeze-drying. Some of the European cryobiology groups are led by Dr. Yuriy Petrenko at the Institute of Experimental Medicine of the Czech Academy of Sciences in Prague, Dr. Alexandra Stolzing at the Loughborough University in the United Kingdom and Dr. Christiani A. Amorim at the Université Catholique de Louvain in Brussels, Belgium. In China, Prof. Gang Zhao leads a cryobiology group at the University of Science and Technology of China situated in Hefei.

Researchers tend to form and organize various societies to share ideas, communicate and connect, and so is the case in the field of cryobiology. The Society for Cryobiology was founded in 1964 in the United States, with Peter Mazur as one of the founding members, with the idea to bring together scientists from multiple disciplines, mainly chemistry, biology, physics, and engineering, to promote research on using low temperatures on biological material. Today it has more than 300 members from all over the world who regularly meet at the annual scientific meeting organized by the board directory. A more European-based cryopreservation society, the Society for Low Temperature Biology, was also founded in 1964 with the general purpose of promoting research into the effects of low temperatures on living organisms and their tissues, cells, and other components. In 2003, they also became a registered charity based in England and have more than 100 cryobiologists from several scientific branches today.

There was one research group that constantly kept popping up while I was researching the field of cryobiology, and it was at the University of Washington’s Center for Cryo-Biomedical Engineering and Artificial Organs, which was established in 2004 and led to this day by Professor Dayong Gao. The group mostly focuses on cryo-biomedical engineering and fundamental cryobiology, the interdisciplinary science and technology of artificial organs, and bio-instruments and micro-sensors for disease diagnostics. As the principal investigator of the world’s leading research group in cryobiology, Dr. Dayong Gao was elected as the President of the Society for Cryobiology. Throughout his career, Dr. Dayong Gao has published over 500 peer-reviewed scientific publications, and I was honored to interview him and two other members of his group, Professor Shen Ren and Professor Zhiquan (Andy) Shu, both of whom were previous Ph.D. students of Dr. Gao. For starters, I wanted to know how they see the position of their group in the cryobiology field today.

Alex: It seems the University of Washington’s Center for Cryo-Biomedical Engineering and Artificial Organs is the mega-hub for cryobiology. Everyone I talk to in the field of cryobiology points to the University of Washington as the “go-to” place in cryobiology and the top 3 places globally. How do you see its position and how does it compare to others in the field?

Professor Dayong Gao: I have been working in the cryobiology and biopreservation research field for over 35 years since I was a Ph.D. student. My Ph.D. dissertation study focused on cryobiology and cryopreservation of human red blood cells under the guidance of Dr. Sui Lin and Dr. Frank Guttman in Canada. I continued my postdoctoral research in cryobiology under the supervision of Dr. John Critser and Dr. Peter Mazur in the USA. Our research center at University of Washington (UW) is just one of the major cryobiology research groups in the world. There are other outstanding research groups in the USA and different nations. Our team work has primarily focused on, first, investigating bio-heat-mass transfer (at both the macro- and micro-scales) and its dominant control mechanisms on cryoinjury and cryoprotection to living cells and tissues at low temperatures, which determine the life-or-death of these biomaterials during cryopreservation, and secondly, developing innovative technology and instruments for the long-term cryopreservation of living cells and tissues which are used for regenerative medicine, tissue engineering, cellular and gene therapy, organ transplantation,vaccine/drug development, disease screening, in vitro fertilization, and conservation of endangered species. Besides, we have been developing novel artificial organ systems for the treatment of end-stage multi-organ-failure disease through fundamental research and the clinical trials at UW Medical Center. We are also developing bio-instruments and micro-sensors for clinical diagnostics. I have been so fortunate to work with many of my teachers, friends, colleagues, and students who have continually helped, collaborated, and supported me throughout my career development!

To study cryobiology, an unique interdisciplinary science, you need knowledge of biology, engineering, physics, chemistry, and medicine at the same time, and our group is one of the rare ones that has all that, with an integrated group of outstanding engineers, physicists, physicians, biologists in our center. We have contineously received funding support from the US government funding agencies, the Bill and Melinda Gates Foundation, as well as other foundations and industries, respectively. University of Washington and my Department leadership supported me greatly and gave me a lot of internal resources to do the research work. This enabled my group to work freely and focus on resolving major issues in the field.

Shen: We are located in Seattle which is a very supportive city regarding biomedical research and we are able to choose between many collaborators here. What I think separates us from others in the field is the multidisciplinary approach we have – cryobiology demands the integration of several scientific fields and experimenting with all of the steps of the cryopreservation process. We are making contributions to all of the steps at the same time which I believe really makes us stand out. A big plus is also our novel single-mode electromagnetic resonance (SMER) rewarming technology, which nobody else uses at the time. It offers us to rapidly and uniformly rewarm our samples with more control over the whole process.

It seems I am really talking with the big leagues in today’s cryobiology. This made me want to ask the youngest and most recent Ph.D. of the group, Professor Shen Ren, to tell me what his current research interests are and how he decided to work in the field.

Alex: Shen, can you tell me about your current research and what led you to it? What do you think your cryopath will be in the future?

Shen: Great question! The first time I heard about cryobiology I didn’t know what it was. I became a part of the group in 2014 when I started my graduate study at the University of Washington with Prof. Dayong Gao. I’ve been working in this field for the past 7 years, mostly on its critical challenges. One of those is utilizing low temperatures to preserve the functionality of biological samples. At -196 Celsius degrees of liquid nitrogen, the rates of biochemical reactions are almost zero. The challenge I’m working on is, how to rewarm the biological material from deep low temperature to body temperature while maintaining its viability and biological functionalities. The water-bath warming is currently the gold standard rewarming method in clinical settings. However, its rewarming rate is too slow, which can cause ice recrystallization that will damage the cells. Moreover, the water bath warming is not uniform and cannot rewarm the biological material simultaneously. It will start rewarming the surface of the cryopreserved biomaterials, but the center will stay cold. The temperature gradient will rupture the biological sample, caused by thermal stress. Thus, we need a fast and uniform rewarming system and that is what I have been doing. One potential solution could be using electromagnetic (EM) power, the same as what’s used in conventional microwaves.

Unfreezing in Snap: Single-mode Electromagnetic Resonance Rewarming

As Shen said, one of the critical problems in cryopreservation is the process of rewarming. If the body cannot be warmed up quickly or uniformly, ice crystals will form and cause damage to tissues and organs.

To simplify, you can imagine a frozen chicken you want to have for dinner. You can put it in the sink to rewarm at room temperature, but this process is quite slow. You can also soak it in a bowl filled with warm water, much like the water bath, and it’ll make the rewarming quicker. However, it won’t warm up equally everywhere, and you can notice the outside of the chicken will melt before the inside. Using a microwave is the quickest and the most powerful way to rewarm the chicken, but you must know from your experience with microwaves how some parts of the chicken get warmed up quite a lot, and even get fully cooked, while the other parts remain completely frozen. The processes for rewarming organs or tissues do not differ a lot and usually use the same techniques. The goal is to rewarm the biological sample as soon as possible, but with the same rate of heating up throughout the whole sample. The usual method of rewarming by using warmed-up water baths simply doesn’t cut it anymore for large samples and rewarming becomes more of an engineering issue.

Single-mode electromagnetic resonance rewarming developed by Dayong Gao’s group is a method of dielectric heating based on Maxwell’s theory in which the temperature of the non-conductive sample can be raised by subjecting it to a high-frequency electromagnetic field. The sample is put in a resonance cavity with an induction coil and the electromagnetic wave is created by an oscillating electrical field. The main advantage of this method is very rapid and uniform heating that can be achieved in a very short amount of time.

Unlike other groups that use multi-mode electromagnetic waves (just like those used in a household conventional microwave oven) for rewarming, Dayong Gao’s group uses automatic single-mode electromagnetic waves. This enables them to automate the wave of a specific frequency and keep it stable throughout the whole rewarming process.

Prof. Dayong Gao’s group seems to have discovered something new and promising, including the improved single-mode electromagnetic resonance rewarming method. Of course, it’s not that easy and the group members were here to tell me all about it.

Alex: What are the benefits of rewarming cryopreserved biological samples using single-mode electromagnetic resonance cavity? How did you improve the problem of rewarming by using this method?

Professor Dayong Gao: Rapid and uniform rewarming is indispensable for preventing deadly ice recrystallization inside and outside cells and tissues during the thawing process. To achieve this goal, I started to investigate the single-mode electromagnetic (EM) resonance (SMER) technology for rapid and uniform rewarming in 1998 at the University of Kentucky. Through the past 25-year continued research at University of Kentucky and University of Washington, we designed and developed a novel SMER cavity to generate a standing wave that then generates a very strong electric field in a very short amount of time. The energy in the electrical field is absorbed by the cryopreserved biomaterials and converted into heat (thermal energy). We took great advantage of water, a dipolar molecule, which is present everywhere in biological systems, to be heated easily because the dipolar molecules can rotate, generating heat by friction under occilating electric fields. How can you guarantee the EM resonance status during the heating process? We developed a pioneering control system to make sure that the heating process is always at EM resonance conditions and the highest electrical energy can be converted into heat. How can you guarantee the different parts in a frozen biomaterial absorb the heat in the same amount to be warmed up uniformly? This is very difficult! We call this “thermal runaway” problem. If the material would heat up differently, some spots would continue heating up at different rates than others. We use specific patented CPAs cocktails to prevent thermal runaway. In addition, we added a control system to locate the sample in the right place inside the cavity and loaded a small amount of magnetic nanoparticles into the biomaterial to utilize the magnetic field energy to enhance the uniform heating. Therefore, both electrical field energy and magnetic field energy are used in the warming process. After years of research, we solved 4 major problems: optimal design of the SMER cavity generating the high strength standing wave, maintaining the resonance throughout the heating process, preventing the thermal runaway, accurately loading the samples into the cavity, all of which ensured rapid and uniform rewarming. We even used larger samples in our cryopreservation experiments and the SMER worked successfully. Several other major cryobiology research groups in the USA and other nations are working on optimal rewarming techniques using either magnetic fields with magnetiic nano-particles or lasers, with significant progress and successes. Coupled with the SMER technology advancement, we are developing the optimal vitrification approaches in cooling and the optimal organ perfusion system for addition and removal of CPAs in organs.

Zhiquan: Rewarming is critical and we need to rewarm cryopreserved biological samples fast and uniform, otherwise the cells and tissues can be damaged by ice recrystallization and thermal stress-induced fracture. We use electromagnetic-assisted volumetric heating which means that the dipolar water molecules will be heated by electromagnetic waves. This might be the best method for rewarming so far. A big challenge is how to control the uniformity of the electromagnetic field itself and use the energy efficiently, and a good way to do that is exactly by using single-mode electromagnetic resonant cavity and dielectric heating together with a focus on optimizing the vitrification solutions.

Shen: Compared to the conventional multimode system, a single-mode operating system can create much stronger and more uniform electromagnetic fields with the same power input. That is our proposed method to achieve fast and uniform rewarming. We also developed an embedded control system to monitor and control what is happening in the system. In contrast, with a multimode system, it is extremely hard to calculate and analyze the distribution of the electromagnetic field. With the established single-mode electromagnetic resonant system, we successfully rewarmed a larger volume of cell suspensions of about 25 mL and some tissues. We continued the hard work on the large animal tissues and organs. …

I then asked the head of the group, Dr. Dayong Gao, to tell me more about some other new promising methods for improving cryobiology that might develop along their single-mode electromagnetic system.

Alex: It looks like everyone in the field is focused on two areas of research – CPAs and vitrification, and rewarming – are there any other approaches that you may see as promising?

Professor Dayong Gao: The other way to stop biological time without lowering the temperature is drying. One way of doing this is using a warm dry gas to get all the water vaporized at room temperature. That’s usually done to plant seeds or some lower organisms like bacteria. For other cells and tissues, we can use freeze-drying (lyophilization). Low temperatures are still used for freezing, but after freeze-drying through a sublimation process, one can store dried samples at room temperatures.

Cryobiologists are also investigating how some animals and insects hibernate and how the biological time slows down without those organisms eating any food for months or years (remaining alive).

Isochoric-cooling cryopreservation to eliminate ice formation is another important and promising approach. Professor Boris Rubinsky of UC Berkeley takes the leadership role in this cryopreservation technology.

The Future of Cryobiology: Scientists, not Fortune Tellers

After learning a lot about cryopreservation and being pulled deeper into the field by my impressive interviewees, I’m more eager to know what the future holds. Therefore, as a final round of questions, I wanted to know what Dayong, Shen, and Zhiquan think about the future prospects and breakthroughs in cryobiology.

Alex: How do you see the future of cryobiology?

Professor Dayong Gao: The development in science, including the cryobiology field, is not linear. Certain scientific discoveries and technological breakthroughs can rapidly advance the field. Before 1949, nobody could even freeze mammalian cells until Christopher Polge suddenly discovered glycerol as a cryoprotectant. After that, researchers discovered dimethyl sulfoxide and other cryopreserving agents for different types of cells. There are still big issues to be solved regarding cryopreservation, mostly the lethal recrystallization of ice when the biological material is being rewarmed. We think the problem can be solved now, in part, by using the SMER rewarming technology, and/or other novel technologies developed by other scientists.

Zhiquan: I think a lot of people are not very satisfied with the speed by which the development of cryobiology is progressing. However, as scientists, we need to work together and I look forward to seeing the progress we will bring in the next several years. Interesting topics that continue developing are the CPAs formulations where the question is if we can learn from mother nature, for example, synthesize any polymers that would mimic ice crystal formation-preventing proteins and sugars naturally found in plants and animals. There are also a lot of open questions regarding electromagnetic rewarming, for example how to establish automatic control of the process and maintain the resonance stability through the process? There also might be some alternative ways to perform biopreservation. Let’s see what we come up with in the next 5 years.

Shen: Organ preservation is the holy grail in cryobiology and after we tackle that, there will be no obstacles to rewarming the whole body. Other than that, different combinations of the CPAs are really interesting and important topics in cryobiology where we still don’t know the optimal solution. CPAs can protect the cells from ice crystals, but can also be highly toxic and cause high osmotic pressure or direct damage to bio-samples from toxicity. We are trying to find out how we can achieve the optimal concentration of CPAs or if it is even possible to do rewarming without any CPAs. I think cryobiology can also be applied in industry and I look forward to seeing more commercialization since it’s only in the beginning stage now.

Alex: When do you think we will see an organ, a small mammal, and a human successfully cryopreserved?

(I want to note here that all three of my interviewees chuckled at my question)

Professor Dayong Gao: I optimistically believe we will see a small organ, e.g. whole ovary or testis, to be cryopreserved successfully within the next two years. If that happens, I see the vital organs being cryopreserved not long after that, but new problems may occur on the way. The more complicated the organ, the more problems you can encounter. The same goes for small mammals. If we can cryopreserve a large human organ, I may do the same for small mammals in the future. However, it is hard for me to comment on this as a scientist, since I don’t know what kind of problems we could find along the way. I can’t predict when any of that could happen. Nevertheless, accomplishing even a small goal brings a lot of hope to people suffering from organ failure diseases, who can greatly benefit from organ cryopreservation, and that’s where we find our motivation.

Zhiquan: People may be able to cryopreserve some organs in the next several years. For small mammals, I don’t believe we could do this in the next 5 years, but maybe in 10 years or longer. For the whole human body, that is still science fiction for me. But, who knows? However, I am sure that we should work hard together and we need more funding support to be able to do more research and experimental work.

Shen: I believe we are on the right track to organ preservation, and I am optimistic that we can achieve the rewarming of a cryopreserved small mammal in 10-15 years. However, it would be a huge jump from a small mammal to a human body, even only from a small mammal to a bigger mammal.People are constantly talking about the whole human body’s preservation, but it is still nearly impossible in the foreseeable future. I would take baby steps and focus on organ preservation at the moment. I was even skeptical about preserving an organ when I joined the research group, but now I am very confident that it will happen in the near future.

And there you have it – the most modern medical future never seemed so close, but so far away.


Epilogue

In my opinion, the field of cryobiology today can be compared to the field of deep learning in 2010 – many of the technologies are “almost there” and are converging. I personally believe that converging the current technologies in cryoprotecants, vitrification, isochoric cryopreservation, rapid rewarming, and noble gas chemistry, in 3-5 years will enable the first “killer experiments”. In cryo, the equivalent of the ImageNet moment in deep learning would be an experiment where a small mammal would be cryogenically preserved and later unfrozen with minimal damage. The transformative potential of this technology is immense and, like deep learning, will give rise to the new industries. Like in 2010 in deep learning, it is probably too early to raise enormous amounts of venture funding to form companies to pursue the applications of this technology. But it is the right time to start funding and supporting academic research in this area to accelerate progress and I made a personal pledge to support and promote this field.

I also predict the massive gap in talent in this exciting field. When deep learning started outperforming humans in image recognition in 2013-2014 and the field of Artificial Intelligence became “hot”, some of the postdocs in the field were getting million-dollar salaries to move from the academia to the industry. We should expect similar talent crunch in cryobiology. There are several groups around the world that demonstrated excellence, dedication, maintained high academic standards, high levels of credibility, and delivered outstanding results despite the “cryo winter” and decades of insufficient public funding. The Dayong Gao group is one of the leading global hubs for cryobiology in the US that is rapidly advancing the rapid reheating technology and deserves recognition and public funding. It is a great time for the governments worldwide to start the race in cryobiology and for the young ambitious academics to choose cryopreservation as the main field of specialization.

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