The Cryonics Institute’s 87th Patient: By Ben Best
The 87th patient of the Cryonics Institute is a man named Theo, who for over a decade had served as President of the Cryonics Association of Australia (CAA) before his recent resignation due to health concerns. In 1990 Theo helped with the cryopreservation of Roy Schiavello, Australia's first cryonics patient. Theo is a 71-year-old retired teacher and father of five children: three sons and two daughters. All family members were supportive of Theo's long-expressed determination to be cryopreserved when his time came.
In many ways Theo received excellent cryonics treatment, but in many ways his treatment left much to be desired. He succumbed to a cancer which began in his prostate and spread to his bones, abdomen and other organs. In October, when Theo asked CI about the possibility of vitrification in Australia, I gave him links to some of the most relevant case reports and told him that I would help with the development of vitrification capability in Australia. Despite assurances by CI's cryobiologist that CI−VM−1 is stable at dry ice temperature, I had worried about the possibility of devitrification until hearing Dr. Brian Wowk discuss the "safe temperature zone" at the May 2007 Suspended Animation Conference. Following my offer of assistance, Theo sent the following message to CI Facilities Manager Andy Zawacki:
Hello Andy: Thanks for the offer to help with vitrification in Australia -- we will look into this in due course.
Now on another matter: can you confirm that my life insurance policy document is in your possession? It may be required in connection with a terminal illness claim which I am proposing to make. Do not be too alarmed by this however. I was diagnosed with prostate cancer a couple of years ago, following which I had the usual hormone treatment, and am now completing a cycle of chemotherapy, which is showing positive indications. However the condition does meet the insurance company's criteria for a payout, which would be most useful to me (allowing among other things the CI charge to be prepaid). So - if you can just confirm possession of the policy document, I will let you know when any further action is needed. Regards - Theo
Theo had several communications with both CI Facilities Manager Andy Zawacki and me in the preceeding weeks, but had not given any evidence of his terminal condition. I first became aware of it when I received a phone call from his funeral director who requested CI's guidelines, and was informed that Theo would not last more than a day. As it happened, Theo lasted four days.
Theo was under home hospice case with several family members providing him with 24-hour observation. His physician happened to be visiting at the moment Theo stopped breathing and pronouncement was immediate. Joe Allan (a CAA Member who belongs to Alcor) and two of Theo's sons placed Theo into a body bag containing ice. Theo had ice above him and below him, with a blanket added for more insulation. The bag was placed into a shipping container built by the Cryonics Association of Australia, with ice packed around the body bag. Theo had been given 25,000 IU of heparin (to prevent blood coagualation) along with clexane (a heparin-like drug), but these were administered eight hours prior to Theo's deanimation.
Clexane has a half-hour half-life independent of the amount administered. The half-life of heparin is generally estimated to be 90 minutes, although at doses of 400 IU per kilogram the half-life of heparin can be extended by as much as one hour. This may have been what Theo's son referred to when he said that clexane assists the action of heparin. I nonetheless believe that more heparin should have been administered at the time of deanimation.
I discussed the possibility of glycerol perfusion with both Joe Allan and Theo's oldest son in case Theo should deanimate on a Friday afternoon. I have not supported glycerol perfusion because of my knowledge that glycerol can do no more than reduce the amount of ice (it does not vitrify) and because of my belief (supported by our cryobiologist) that freezing damage is worse than up to three days of the cold ischemia suffered by a patient packed in ice. Embalmer's pumps can produce terribly high perfusion pressures. Joe was not convinced that his pump is functional. Two funeral directors in Australia had experience perfusing cryonics patients with glycerol, but one was in China and the other had stopped working in the funeral industry and could not be located.
Theo deanimated a half-hour before midnight on Thursday, February 28 (East Australia time), but was not shipped from Australia until Friday, March 1st -- a 37½ hour wait. After a 16 hour flight to Los Angeles (which included a one hour stopover in Sydney) he sat in the Los Angeles airport for 6 hours, had a 6 hour flight to Chicago, waited in Chicago for 7½ hours and arrived in Detroit Sunday morning at about 10 am after a flight of just over 2 hours from Chicago. All flights were by United Airlines, which has a hub in Chicago. I could find many flights that would have gotten Theo into Detroit on Saturday evening if there had been a change of airlines in Los Angeles.
Working with Theo's oldest son (who told me that he is more optimistic than any other family member concerning cryonics), I tried to arrange a flight change. I was not able to reach Theo's funeral director and he did not return my call. Theo's funeral director never communicated with CI's funeral director -- not even to inform him that the patient had been shipped. The Australian funeral director may have been unfamiliar with international shipping, and I suspect that his enquiries with various authorities triggered the involvement of the US Department of State. We at CI, CI's lawyer, and CI's funeral director received numerous phone calls from a woman in the US State Department who was asking many questions about CI's procedures and legal authority. It was through these phone calls that we were informed for the first time that Theo had been pronounced dead more than 12 hours earlier, and it was the woman at the State Department who first informed us of the flight schedule.
Pickup at the Detroit airport was delayed over an hour because the Australian funeral director had not FAXed a copy of the death certificate or transit permit to CI's funeral director. These documents were found with the shipping box. (These documents must have accompanied the box or else Theo could never have been shipped. Perhaps the weekend customs officials at the Detriot airport are not as experienced as the weekday staff.)
I was enormously worried about possibility of all the ice melting during the long shipment time from Australia. Surprisingly, when the shipping container was opened, the ice was remarkably well preserved, and very little of it had melted. Jim Walsh, CI's funeral director, was very impressed with the insulating effectiveness of the Cryonics Association of Australia's shipping box. But soon after Mr. Walsh had placed Theo on the table for surgery and perfusion, he observed that Theo was hard and stiff. Theo had been frozen.
I had been told that Theo was held by the Australian funeral director in a 2ºC to 4ºC cooler to keep the ice packed around Theo from melting. When I had tried to reach the Australian funeral director on the phone to change flights, an assistant told me that Theo had been taken for storage in a cooler at the airport the night before the flight. Mr. Walsh was convinced that Theo had been frozen in one of the coolers in Australia. I suspected that Theo may have been exposed to subzero Winter temperatures during the 7½ hours at Chicago. If I was correct, there would have been a considerable amount of refrozen water, but I was told that there was very little evidence of this -- which supports the argument that he was frozen in Australia.
Human body fluids contain a variety of salts, some of which would not form a frozen solid above −20ºC to −50ºC. Although Theo was stiff and hard, he was not rock hard. Mr. Walsh suggested that the head/skull may have provided insulation for the brain and that a perfusion should be attempted. I was dubious, but I agreed that an attempt should be made. My expectation was that the blood vessels would have been so broken by ice that no flow would be possible.
The tissue was soft enough for Mr. Walsh to cut, and Theo had large vertebrals such that both vertebrals and both carotids could be cannulated. When perfusion was begun there was reasonably good venous return from the jugular veins, showing that the large blood vessels had not been damaged -- or, at least, not as much as I had feared. This makes sense, because when animal tissues are cooled slowly, the initial ice that forms is either inside blood vessels or in spaces between cells. As long as the temperature did not get too low there should not be enough ice to break blood vessels. And if blood vessels were broken, the smallest ones would be broken first, and the largest ones broken last.
The perfusion began shortly after 2pm with 10% ethylene glycol. Fifteen minutes later the patient had received 3½ liters at an average pressure of 80 mmHg. Three liters of 30% ethylene glycol was then added to one liter of 10% ethylene glycol in the reservoir. Three liters of this solution was perfused with an initial flow rate of 930 milliliters/minute and line pressure of 104 mmHg, and a final flow rate of 880 milliliters/minute and line pressure of 116 mmHg. The patient's head had swollen and the resistance to flow was becoming very evident. Four liters of 70% CI−VM−1 was added to the one liter of ethylene glycol solution remaining in the reservoir and perfusion was resumed. Four-and-a-half liters of this solution was perfused with an initial flow rate 470 milliliters/minute and pressure of 76 mmHg, and a final flow rate of 129 milliliters/minute and line pressure of 129 mmHg. The resistance to flow was becoming so great that the decision was made to stop at 3pm. The perfusion data is approximately (ignoring dilutions) summarized in the following table.
CI's 84th and 86th patients had received 3.5 and 5.0 liters of 10% ethylene glycol (respectively), 5.0 liters of 30% ethylene glycol, and 15.0 and 12.0 liters of 70% CI−VM−1, respectively. In usual cases it is better to avoid increasing solution concentration too rapidly if osmotic shock is to be avoided. In this case, the greater risk was tissue edema preventing perfusion, which is what happened. If the more concentrated solutions had been introduced sooner there probably would have been less edema, and more of the vitrification solution could have saturated the brain.
No burr holes had been made and no refractive indexes were measured. Theo had requested that his body be perfused, but that simply was not feasible under these conditions.
|Jim assists Andy putting Theo into cooling box|
The patient was given the same treatment as any properly vitrified patient would receive. An enclosure containing dry ice pellets and isopropyl alcohol was placed around the patient's head, with his neck resting on the edge of the enclosure and the rest of his body wrapped in a sleeping bag. The patient was then driven to the CI Facility where the enclosure was removed from around his head. Jim Walsh assisted Andy in placing Theo into the computer-controlled cooling box for cooling to liquid nitrogen temperature.
In the first fifteen minutes of cooling box cooling brain surface temperature rose from −30ºC to about −22ºC before falling. Brain core (naso-pharygeal) and body temperatures were up to about 5ºC, but both fell steadily, even in the first fifteen minutes. Oddly, the body temperature fell more rapidly than brain core temperature. Only after four hours and forty minutes did brain core temperature drop below (and remain below) body temperature. In other cases the body temperature drops very slowly compared to any head temperature. The placement of the temperature probe in the chest must have been superficial rather than deep.
|First 5 hours||Annealing|
Brain surface (skull) temperature was cooled to −115ºC in just over two hours, cooled more slowly for another hour to −120ºC, and then held at −120ºC for about fifteen hours while the brain core temperature dropped more slowly to approach −118ºC. This was followed by an "annealing" step in which brain surface temperature was allowed to rise gradually for an hour. At the end of this time brain surface temperature rose to nearly −116ºC while brain core temperature rose to about −117ºC. This step was intended to achieve more temperature uniformity of the brain, which is intended to reduce thermal stress on cooling. Following this step the gradual cooling to liquid nitrogen temperature (initially programmed to take 101 hours) was begun.
|False alarm of power failure|
Twenty-seven hours after the patient had been placed on the cooling box the alarm sounded and phone numbers were called by the auto-dialer on the cooling box controller, signalling that there had been a power failure. But there had been no power failure in the building. I changed controllers, changed computers, checked the cables and the Uninterruptible Power Supply (UPS) seemed to be functional. When I clicked on the "Reset" button of the dialog box giving the warning, the box would re-appear. Then it would not re-appear. I was mystified.
Only after the patient was removed did I notice that the power cord had not been securely plugged to the wall socket. It had been pulled loose somehow. Andy normally wires plugs into the wall sockets for the vacuum pumps, and this practice seems adviseable for the UPS plug in the future.
While I was changing controllers, PCs, etc., I was manually adding liquid nitrogen by pushing a button controlling the valve. With the computers and controllers off I could only guess how much liquid nitrogen I was adding, and I added a bit too much. But I also became suspicious of how much the skull temperature had dropped. There had been no burr holes in this case and I had not paid careful attention to where the thermocouple was placed under the skin of the skull. I began to think that it was on the back of his head, and that liquid nitrogen might be pooling near the thermocouple.
When opening the cooling box at the end of cooling I saw that the thermocouple was on the right side of Theo's head, the side closest to the spray bar. His head was close to the spray bar because, being tall, he had been positioned diagonally in the cooling box. Proximity to the spray bar may have affected the chest temperature as well. In the future, when tall patients are placed diagonally in the cooling box we should ensure that the upper body is away from the spray bar.
Fifty hours after using ambient for control
(yellow is ambient temperature)
I decided to make the ambient temperature in the box the controlling temperature, rather than the skull temperature. I had not done this for quite a while, having decided that ambient temperature causes too much opening and closing of the valve. As it turned-out, it did not result in much more valve activity than using the skull temperature as the controlling temperature.
But an unexpected effect was that 40 to 50 hours after changing the controlling thermocouple the head and body temperatures were nearly 15ºC lower than the temperatures I was targeting. This may have been due to the closeness of the head -- and the top of the body (body temperature being measured as thermocouple in chest) -- to the spray bar. When it became clear to me that the liquid nitrogen temperature would be reached in the wee hours of Friday morning rather than during the day on Friday, I changed the program to accelerate the cooling to finish Thursday afternoon. This would not critically affect thermal stress or cracking because the thermal expansivity declines with temperature -- meaning equivalent temperature changes at the lowest temperatures result in much less thermal stress than the same temperature changes at higher cryogenic temperatures.
But close to the end, the liquid nitrogen must have been having a flooding effect because all of the temperature probes fell rapidly to liquid nitrogen temperature. We moved Theo into the cryostat earlier in the afternoon than I had planned -- finishing at about 1:30pm.
|Last hour||Last 65 hours|
For the first time since we began use of the cooling box I paid very close attention to the amount of liquid nitrogen being consumed. About 560 gallons (2120 liters) of liquid nitrogen were used to cool Theo. About one quarter of this total was consumed in the first two hours, when the valve was open almost continually in an attempt to cool as quickly as possible to approach glass transition temperature (Tg) (solidification temperature) in order to prevent devitrification. This compares to the 420 gallons (1590 liters) used on the weekly fill of all of the cryostats.
With every patient we learn new things about how to improve and not repeat mistakes. This is always good for future patients, but feels very tragic with the patients with whom we learn our lessons. With so few cryonics patients in the world, cryonics patients are too often the pioneers with the arrows in their backs. That is the price of being a pioneer. Theo was certainly a pioneer, and I hated to see any arrows in his back. I respect all his dedication and years of service to cryonics. I hope that, despite the problems, he has been well-enough preserved to be reanimated to his full youthful potential someday. And to receive the appreciation that he deserves.