Are you a VC doing cryo start-up due dilligence? A researcher trying to keep up? Did you sign up for cryopreservation and you're estimating your revival science-based prognosis? This post is for you
The most important contribution of this paper is demonstrated rapid warming on a human organ scale. The cooling part, vitrifying multi-liter volumes of M22, is actually easy because M22 was originally designed and demonstrated for that purpose more than 20 years ago. By coincidence, I first showed that two liter volumes of M22 could be vitrified without ice formation or cracking at the University of Minnesota in 2005 during the Society for Cryobiology meeting there. ( “Toward large organ vitrification: extremely low critical cooling and warming rates of M22 vitrification solution,” Cryobiology 51, 362 (2005)). One of the slides from that talk, a photo of a vitrified 2 liter volume of M22, has been on the web for 20 years.
Although not in refereed scientific literature, Alcor was the first to demonstrate a decade ago by CT scanning that large organs (a human brain) could be vitrified without ice formation using M22. The U of M work is certainly great and a major milestone, but the cooling problem hasn't really been a problem with M22 provided that adequate concentrations reach all parts of organs. That was what the solution was designed for.
Thank you so much for your insight, Brian! Yeah, I agree that cooling is not that much of a deal breaker anymore (wow, your work really did preceed it all!). But that paper clearly states "towards human organs" which is a huge deal for conservative academic environment;) And the nanowarming is the key tech right now, would you agree?
Nanowarming is certainly a new and important technology, but it's difficult for me to say whether it alone is going to enable reversible human organ cryopreservation. Dielectric warming remains a strong alternative. Dielectric warming was shown able to warm human organ-sized volumes of cryoprotectant solution decades ago ("Rapid and uniform electromagnetic heating of aqueous cryoprotectant solutions from cryogenic temperatures," Cryobiology 27, 465-478 (1990)). It was recently used for rabbit kidneys in a vitrification-transplant model. I'm now building a 10 kilowatt system for human organs. High intensity focused ultrasound is a third method, although much less developed. All warming methods have different pros and cons. Warming equipment and expertise is still so complex and customized that the best warming method is arguably the method that a given group is best equipped and experienced to use.
The present situation isn't so much that cryopreservation has been stuck on the problem of volumetric warming, it's that organ cryopreservation has been stuck on other problems for so long that volumetric warming was a mostly theoretical concern for the future. The technology for preparing organs for cryopreservation has finally advanced enough that volumetric warming can now do more than just make impressive graphs. Interest has grown accordingly, including in legacy methods.
I do not quite understand why you say that "It shows that the minimum cooling rate decreases with volume, which is not intuitive" when discussing Fig. 8 of the first paper. Perhaps it is because the graph should actually say what the figure title says "achievable cooling rates". It is quite intuitive that the larger the object, the longer it takes to cool it, most people would say so when asked if it a large pot of hot soup would cool faster than a small bowl.
The most important contribution of this paper is demonstrated rapid warming on a human organ scale. The cooling part, vitrifying multi-liter volumes of M22, is actually easy because M22 was originally designed and demonstrated for that purpose more than 20 years ago. By coincidence, I first showed that two liter volumes of M22 could be vitrified without ice formation or cracking at the University of Minnesota in 2005 during the Society for Cryobiology meeting there. ( “Toward large organ vitrification: extremely low critical cooling and warming rates of M22 vitrification solution,” Cryobiology 51, 362 (2005)). One of the slides from that talk, a photo of a vitrified 2 liter volume of M22, has been on the web for 20 years.
https://web.archive.org/web/20051220043911/http://www.alcor.org/sciencefaq.htm
Although not in refereed scientific literature, Alcor was the first to demonstrate a decade ago by CT scanning that large organs (a human brain) could be vitrified without ice formation using M22. The U of M work is certainly great and a major milestone, but the cooling problem hasn't really been a problem with M22 provided that adequate concentrations reach all parts of organs. That was what the solution was designed for.
Thank you so much for your insight, Brian! Yeah, I agree that cooling is not that much of a deal breaker anymore (wow, your work really did preceed it all!). But that paper clearly states "towards human organs" which is a huge deal for conservative academic environment;) And the nanowarming is the key tech right now, would you agree?
Nanowarming is certainly a new and important technology, but it's difficult for me to say whether it alone is going to enable reversible human organ cryopreservation. Dielectric warming remains a strong alternative. Dielectric warming was shown able to warm human organ-sized volumes of cryoprotectant solution decades ago ("Rapid and uniform electromagnetic heating of aqueous cryoprotectant solutions from cryogenic temperatures," Cryobiology 27, 465-478 (1990)). It was recently used for rabbit kidneys in a vitrification-transplant model. I'm now building a 10 kilowatt system for human organs. High intensity focused ultrasound is a third method, although much less developed. All warming methods have different pros and cons. Warming equipment and expertise is still so complex and customized that the best warming method is arguably the method that a given group is best equipped and experienced to use.
The present situation isn't so much that cryopreservation has been stuck on the problem of volumetric warming, it's that organ cryopreservation has been stuck on other problems for so long that volumetric warming was a mostly theoretical concern for the future. The technology for preparing organs for cryopreservation has finally advanced enough that volumetric warming can now do more than just make impressive graphs. Interest has grown accordingly, including in legacy methods.
I do not quite understand why you say that "It shows that the minimum cooling rate decreases with volume, which is not intuitive" when discussing Fig. 8 of the first paper. Perhaps it is because the graph should actually say what the figure title says "achievable cooling rates". It is quite intuitive that the larger the object, the longer it takes to cool it, most people would say so when asked if it a large pot of hot soup would cool faster than a small bowl.