Improving Cryopreservation Technology at Alcor
Posted by Jeriaska on October 17th, 2007Alcor Chief Administrative Officer Jennifer Chapman and Chief Operating Officer Tanya Jones
Tanya Jones has participated in the cryopreservation of over half of Alcor’s 78 cryopreserved patients. She started her career at the life extension organization over a decade ago and her experience as the Chief Operating Officer is effectuating innovative change within the organization. As the leader of Alcor’s emergency response capability, she is actively responsible for elevating the level of care. She shared details of present-day initiatives to provide the state-of-the art in cryonics technology at the 7th Alcor Conference.
The following partial transcript of Tanya Jones’ 7th Alcor Conference presentation “Improving Cryopreservation Technology at Alcor” has not been approved by the author. DVD sets of the conference can be purchased at the Alcor website.
Improving Cryopreservation Technology at Alcor
We have heard a little bit this morning from Brian and from Steve what the elements of a cryopreservation are. I am going to review them here briefly because a lot of the initiatives we are going to be talking about and showing you during the tours tomorrow relate directly to improving stages of the cryoprotection procedure. The most important thing involved in providing quality care to one of our patients is that we be on site and prepared at the moment of cardiac arrest. The moment the heart stops and legal death is pronounced, we need to move quickly to protect the viability of the brain.
Proximity and preparation are critical. Those who have a sudden death situation where we are not informed or we are not on sight don’t receive this level of care because it becomes more damaging to even try. In the ideal cases, stabilization involves preliminary surface cooling. Cooling is the very first thing that we begin to do. Cardiopulmonary support is the next step, as distinguished from cardiopulmonary resuscitation. It is not our intention to wake these people up today. We want to stabilize their tissues so that they can be cured and repaired at a later date. This involves re-initiating circulation, installing an airway if there is not one in place, and beginning oxygenation. We also administer a long series of medications that reduce the damage that is caused through ischemic mechanisms once the heart stops, the oxygenation is stopped and the energy stores in the cell are depleted. Once that is complete, we do a surgical procedure whereby the arteries and veins in the femoral region are cannulated, and the blood is washed out and replaced with a short-acting organ preservation solution. This is very similar to what hospitals use for things like kidney transplants. It buys us somewhere between 24 and 48 hours to get our patients to Arizona, assuming for a moment that they are not in this state.
This is particularly critical because anytime you have to cross a border, be it state or country, there are extensive paperwork requirements that are needed to ship human remains. Though they are anatomical donations, they are indeed human remains. We often get our cases on Friday evenings right after the vital statistics office is closed. Don’t do that if you can avoid it, because then we sometimes cannot get the paperwork until the next day or a couple of days later. As soon as we have the paperwork in place, then we can ship them via a commercial carrier or charter airline to Arizona for the cryoprotection, the cooling and the long-term care.
Some of you were here last year and heard us talking about some of the new projects. Some of them are still in the planning phase. They have moved a lot farther over the course of the year. We have established, as Steve spoke to, our cardiopulmonary bipass lab and are beginning some serious research initiatives. This will allow us to come up with new mechanisms to initiate the stabilization and the cryoprotection to provide better care to our patients. Also critical is developing the tools that we need. If the research tells us one thing, we need to be able to implement it in our human cases. This is particularly tricky because people like Greg Fahy and Brian Wowk work on rabbit kidneys, which are about this big. Translating that to the size of a human is kind of challenging. We are in the process of developing an improved whole-body vitrification system to meet the requirements that have been established in Greg’s lab to reversibly cryoprotect organs to -130 degrees. We will be showing you that in addition to talking about it here. The other aspect is improving the stabilizations. The better care that you can provide as soon after that heart stops, the better the cryoprotection is going to be. We are developing new tools for that that we will be covering as well.
Let me begin with the whole-body profusion system. This is developing into a very nice system. Until this system is deployed, every aspect of cryoprotection has been done manually. Someone has to sit at the computer and monitor the pumps. Now we have a system where we can implement the protocol extremely quickly. Even if we decide through the research tomorrow that we need to change what we are doing in the operating room, this system is sufficiently flexible that we can implement the new control processes in a day or two – it will be very, very rapid. We will have the system programmed for alarm conditions. It can anticipate if the pressure gets too high or too low, if the swelling starts to begin in a patient and you are starting to see edema, and tell us when we are approaching those conditions so that we can adjust the protocol to prevent those alarm conditions from being a serious problem. We are going to be tracking a lot more data than we have before. It’s got extremely advanced data collection. Every single piece of information that that system is tracking is going to be documented. This is very important. That way we can analyze each case and begin to compare cases against each other, which can be tricky because the circumstances of death vary so much, the conditions under which people are cryoprotected vary a lot. But every once in while you get a couple of cases that are under similar circumstances, and if you have the data you can start comparing the quality of care.
The system is going to have automatic report generation, which is actually one of my favorite features, and it has graceful failure modes. The entire system is designed so that if one part fails, you can go in and swap out that part without impacting the cryoprotection or the patient care as a whole. That is the manual control capability, which we consider to be fairly important, because you never know when something is going to go wrong. It is going to have an intelligent user interface, which right now our current system does not have.
This is what it looks like. Cryoprotection is a two-step process where you take a certain amount of time to reach 50% concentration and then you try to ramp up to 100% as quickly as possible. If we are not getting as good cryoprotection in the early stage, the system will be able to adjust to the ramp automatically. Or if it is going a little too fast, we will be able to slow it down automatically. We also have process refractometers that are going to be directly monitoring the cryoprotectant uptake by the tissues. By monitoring the cryoprotectant uptake in particular we are interested in the fluid balance: the water in the body. How much water is being taken out, how much cryoprotectant is going in. This is going to be particularly important in patients with slightly longer ischemic times, slightly longer transit times, because they swell up. Although this is an experimental system, we will be able to figure out whether it is a good idea to increase the ramp, get more cryoprotectant in, to see if we can outrun that swelling that sometimes makes you stop a cryoprotection before you have 100% of the targets that you want to achieve. As I mentioned before, we will be able to have any kind of protocol we want.
The circuit diagram from our system shows that we can both cool and rewarm in very linear fashion. As you get to colder temperatures, you see a little bit of a deviation between what is going in and the temperature of the circuit, but it does not seem to be too significant for our purposes. This is how the pressure is being controlled. It gives you a sense of what the system is capable of. It takes awhile for the system to calibrate itself, but we started at zero and moved it up to 25 RPM. You can see it takes a moment for the cycle to establish itself. The computer has to go through an entire cycle before it registers the temperature. This black line is the system pressure. Say we drop the RPMs because there is something going on that we want to put a stop to, the pressure still registers high because it takes the algorithm a full cycle to respond, but you know as a safety factor that pressure has actually dropped. It does not wait. Even though it registers a little bit high at the beginning, it’s not really. All of these processes are in place right now.
The alarm conditions are pretty obvious if you think about it. We need to know if the temperature is off. The cryoprotection happens between 3 and -3 degrees Celsius. So what happens if we are deviating out of that range? It’s unusual, but it could happen. Pressures are critical because you only want to profuse the body at profusion pressures. So, what happens if it’s going way up? You have to slow down your pumps. We know the cryoprotection uptake and flow balance. For the system there are alarm conditions as well. We don’t want to pump air into a patient. Everyone can imagine, that’s pretty bad. So there is going to be independent bubble protection on both the arterial and venus sides.
We are also going to be monitoring all the fluid levels and all of the reservoirs. Everything that is going on with the computer system, we are recording, and that includes the manual changes. If we decide to override the system for some reason, then all of that will be recorded. My favorite: perform the cryoprotection, push a button, print the report. This gives you everything that you’re going to need. It doesn’t tell you how the surgery went, but it tells you everything that the computer-controlled system did with graphs and all the data you could possibly want.
We’re pretty excited about this. But the perfusion system is not the whole of the croprotection process. We have also been rebuilding the patient enclosure. The lids maintain an internal temperature that is appropriate to the cryoprotection. It is a very stable temperature. We circulate nitrogen vapor around the patient to maintain the outside temperature, in addition to pumping the Perfusate in at the appropriate level.
We have instrumentation over this table when it is finally complete. It is all going to be mounted to provide for a slightly less hazardous environment for the personnel. There are not nearly as many cables to trip over in the operating room. You will not be able to see this when you go to the lab tomorrow, but this is a very radical design in comparison to our previous one. During the cooling stage, rather than just having the patient just lying on an operating table, relying on the perfusion and the cross-current of nitrogen vapor to cool the patient, we have decided to take one of our whole-body pods and actually cool the table itself, so that if you pull the lids off to do the surgery it is not going to impact the temperature that the patient is at.
As an added benefit, it also allows us to test whether or not the patient is going to fit in the whole-body pod. We have only had one case where the person did not fit, but it was extremely awkward. We had to run out and get a pod produced at the last moment. The patient was not harmed, but he was sitting around in the cooling dewar for a little longer than we like. This is what the top looks like. This is where the patient goes. You can see there is a cradle for the pod itself to sit on, but there are also fans. We are circulating the nitrogen vapor around the body this time.
An additional intent with this system, one of the reasons why we spent so much time working on the design of the cooling stage and the nitrogen circulation is because we would like to use it to implement the first stage of the deep cooling. Your patient is at a much more stable temperature before you start with putting them into a pod and moving them around. It is very critical when the cryoprotectant is in there and you are at -3 degrees, you don’t want to spend too much time there, because there is a trade-off between time, trauma and toxicity of the cryoprotectant. It puts the patient in a much safer place for handling. It will also give us a significantly faster temperature to set. We tested the previous version down to about -80, we made some tweaks, and we are pretty confident that this system once we begin testing will go all the way down to -110. We are still working on it. It’s not quite done, but it is getting extremely close.
The second aspect I mentioned was stabilization. Stabilizations are very critical. We know what needs to be done there, with the exception that some of the medications still need to be investigated. We built a new, collapsible ice bath. It’s based on a frame that is used by EMS personnel to do airlifts off of mountains. Somebody gets trapped on a hill, this is what they use to take them out in a helicopter. We had to modify it slightly, but it works. It has a new insulating liner that will keep the patient colder for a much longer period of time. It uses an insulation called aerogel. Early tests indicate that it will hold a patient at zero degrees for five days. We are going to use this to insulate a shipping container for air shipment after the stabilization is complete, so it was important to us that it last for a really long time just in case we encounter problems in shipping. It does seem to work.
We are also still working on the liquid ventilation system, the perfusion cooling through the lungs. It is intended to implement an extremely rapid cooling in advance of the blood washout. We are still working on that and we hope to have that to show next time. The other thing that we have been working on is a new perfusion system for the field washouts. We have come out with a new system. It is lighter and more elegant than our previous design. It uses an integrated system that puts the heat exchanger, the filters, and the pumps all in one neat package. What this has allowed us to do is significantly simplify our perfusion setup. It is going to allow us to put the entire circuit and the Perfusate into one box that fits on an airplane. All you have to do when it’s time to set up for a case is open up the case, connect your cold water source, connect your patient, de-bubble him and cool the circuit. It is going to significantly improve the training required to ready for a field washout.
We are excited about the potential of this device to improve our washouts. It has independent air removal for both the arterial and the venus sides. It has bubble detection and also an auto-stop so that if air is detected in the lines, nothing gets into the patient. We will still have the soft-sided reservoir. That has its advantages. It will also have an arterial jet valve. This is because the pump that we are going to be using for this system is a little bit different from the one we were using before. It’s a centrifugal pump. It has a little risk associated with reversing the flow, so having the valve on there prevents that. We are also in the process of completely reorganizing our stabilization kits. We have been using these kits for at least the 17 years I’ve been doing cases, and they just continue to grow. It’s been a long time since we overhauled things, and what we are trying to do is make things more efficient and more effective simultaneously. We are reviewing all of our procedures and processes for maintaining the regional kits. We want to build these new kits and give them to everybody all at once.
One of the biggest goals that I had when looking at how to redesign these, I wanted to ensure that now that we have the transport vehicle, the surgical unit, that’s two people driving a thousand miles. They are not necessarily going to have enough time to get to a patient’s bedside. Plus, there are still regions we cannot get to using a vehicle. So I want to be able to put two people onto a plane, get them to a patient’s bedside with no worries about possibly having to check an extra bag if it’s a holiday weekend. So what we’ve done is redesign the kits so that even once we add all of the new equipment that we are talking about, it’s an ice bag and three boxes. One of them is the perfusion system. That’s all completely integrated. The old kit, big bulky and really hard to ship sometimes in an emergency. The new kit will be significantly improved.
The other aspect of this is our stabilization network. We have lots and lots of people who have generously given their time to learn about our procedures and our protocol. Many of them are people like you, cryonicists, who want to help. So, we have done a lot of training over the years, but we just don’t have very many cases. It’s really hard for someone who comes in, spends a couple of weekends training, but then you sit around for a couple of years. So what we are going to do is provide realistic training environments for our stabilization team. We are going to recruit new medical personnel. Once we have the tools it should be a relatively straightforward matter to improve the quality of the personnel.
Just to give you an idea of how many regions we are talking about, these are our top five states: California, Arizona, Florida, Texas, New York. That’s over half of our membership. These are our official regions. New England has one, Texas has one. But where could we go if we were using transport vehicles? How many transport vehicles do we need with our arbitrary limit of 1000 miles? Right now we would need six to cover just the United States outside of Alaska and Hawaii. I think I would really like to set up a facility in Hawaii. Those three members really need support. But we are just looking at the U.S. because it was an easy graph to do. Six transport vehicles would support the 48 contiguous states. But that’s not really realistic. Who wants to drive a thousand miles? Then you’re standing around, it’s hurry up and wait. So bringing it out to about a 500 mile radius, which is still not a pleasant drive, we’re already looking at ten transport vehicles in the U.S. It is a bit of a challenge how we deploy our kits, where we deploy our kits, and how we engage them in training.
What we are going to do with this information is we are going to finish the projects that we have in progress. We are going to test the new equipment, build and deploy 14 stabilization kits. These are ten to go to the regions, UK, Australia, a couple to Canada, and the rest around the United States. We are going to have two spares at the lab so that people, when they are being trained, are going to be trained on the precise equipment that they are going to be using in the field. We are going to construct a second operating room, and while we revise our training protocols and our manuals we are going to be doing realistic training that will likely involve either cadavers or large animals, because otherwise how are you going to teach someone how to do a femoral cutdown? I can teach someone how to suture without using anything difficult, but I cannot teach you how to place the cannula. The only way to get that kind of experience is to do it. Then we are going to test, improve and deploy, then we’re going to start over, because that’s just the way these things go.


October 25th, 2007 at 9:52 am
Tanya always looks so cute! When I first met her at a party in LA I mistook her for being my age, even.
January 5th, 2010 at 2:46 am
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