X-Message-Number: 3088 Date: 09 Sep 94 00:54:02 EDT From: Mike Darwin <> Subject: SCI.CRYONICS On technology I have no quibble with Bob Ettinger's major point; a personal or organizational assessment of cost-benefit must be used in applying procedures. As I have said in the past, we differ here, and that is fine and to be expected. There however some specific points in Bob's post I'd like to respond to. State-of-the-art does not mean perfect. It just means meeting the community standard within the framework of a given discipline. State-of-the-art heart surgery doesn't guarantee success, or even mean that patients are uninjured by the procedure: in fact, it is little know but still true that the majority of people who undego heart-lung machine support suffer measurable, serious and long-lasting cognitive and/or emotional impairment. Hardest hit or those with low IQs and those who notice it most (complain the most) are those with high IQs (and the need for mathmatical reasoning: mathmeticians and accountants complain bitterly about post-pump deficits). Still, there is state-of-the-art heart surgery (or bypass). I just yesterday talked with a friend who is also a sales rep for a major biomedical company. She told me (with horror) that hospital X just bought all the last of the bubble oxygenators as a cost containment move and was going to pump patients with them. It was then my turn to react in horror and I said exactly this: "Bubbler oxygenators! Bubblers! Christ! You've got to be kidding! I wouldn't pump one of my dogs with one of those things....! Bubblers were state-of-the-art a few years ago, and in fact at Alcor we pumped all our early dogs and humans with them. But not now. Why not? Because they create microemboli at very high rates compared to membrane oxygenators. In fact, you can sit and watch the retina get progressively infarcted during by pass by giving boluses of fluroscein dye and looking at the retinal circulation wih UV light. Later bubblers were a big improvement over the first Travenol wire wool and vinyl foamers. Membrane oxygenators are a better still -- and result in less post pump deficits than bubblers. When I speak of state-of-the-art perfusion I mean that we use perfusion techniques which are clinically accepted and that our end point: recovery of animals without gross deficits from the reversible part of the procedure is a scientifically and medically defensible one. The problem (as I see it) with the alternative is that you have no feedback. Clinical bypass has evolved to minimize air emboli, minimize particulates, provide good metabolic support, inhibit clotting and activation of the immune/inflammatory cascade, and allow for uniform and rapid core cooling. The problem with not following those rules is that you can do a lot of harm. You can pump air into the circulatory system rendering large areas of tissue inaccessible to cryoprotectant, you can plug vessels with debris from clots, platelet aggregates, and, most of all, with dirt and precipitate in your perfusate. I use reagent grade glycerol and medical grade water because they constitute a floor on quality. Some USP glycerol I've gotten has an amber cast -- it is yellow with aldehydes and who knows what kinds of other impurities. Yes, they cost more, but short of running in-house analysis on every batch I have no way to be sure of quality. As an example, I use distilled water from a commercial supplier for dialysis on my dogs. I've had some very sorry experiences with these guys: sometimes when the RO membrane goes down (virtually nobody really steam distilkls water anymore!) they don't bother to deal with the problem right away or pull the bottles that got filled when the alarm didn't go off. After all, its only distilled water most of which is used for drinking or washing glassware -- hardly a life or death matter now, is it? This is what I mean by state-of-the-art. It means using generally accepted standards to carry out procedures. Where our procedures overlap those of medicine I tend to err towards the conservative side. Bob also says that use of prescription drugs (as he reads the law) is illegal. I would like to know why he thinks this. It is true that certain drugs are controlled and cannot be *posessed* without a prescription and can only be dispensed on order of a doctor with access to "triplicate" forms. However, most medicines do not require triplicates and the use of "prescription drugs" on cadavers for non medical purposes does not constitute "dispensing." You can't dispense a medicine to a corpse. In any event, there are two easy ways around this problem, both of which I use: 1) Get a doctor to write the initial prescription or to serve as medical director. All any wholesale drug house requires is an MD to accept responsibility for the product. If you are ordering controlled substances, then the MD needs to have a DEA certificate. And, if you are ordering Schedule II drugs your MD needs to have triplicates and to exercise control over the drugs to insure they are dispensed and handled properly in accordance with state and federal narcotics laws. 2) Buy medical product as nonmedical product. For instance most medical consumables can br bought non-sterile. You can then sterilize them yourself. Most medications can be prepared in house in sterile dosage form and still not qualify as "prescription drugs." A key issue here is intent. For instance, penicillin, syringes, ivermectin, levamisole, sterile D5W for IV administration -- these are all items which are prescription drugs. And yet, I can order them through the mail as an individual from Omaha Vaccine Company or Veterinary Concepts without a prescription: providing I'm going to use them on my cows or horses and not on my neighbors or my kids! Similarly, I can (and have) gone across the border and brought injectable drugs back with me and declared them at customs. And, as long as they are for personal use, this is perfectly legal. In fact, we buy some of our lab antibiotics down there because it is so much cheaper. If there is any item which CI needs which it fears to use because it is a prescription drug, let me know. I'll see to it that you get it in stable, sterile form with a label that reads: For post-mortem use in human cryoprservation ONLY. Not a drug or medicine for human or veterinary use. Finally, Bob questions the utility of spending money on TBW dog research. I've already responded to Dave Pizer on this point, but a fe more thoughts are worth laying out on the table because they dovetail with the points above: 1) We (Alcor, TT, BPI) have the overhead of maintaining a facility capable of doing human cryopreservations. All of these organizations use medical-type bypass procedures and so that means the overhead associated with them: a building, analytical equipment, supplies which outdate, bypass consumables, etc. The base cost of maintaining this capability (just in terms of the physical part of it) is high regardless of whether you use it every year or every day. 2) By doing research I have found that I attract lots of good quality people I wouldn't have otherwise -- they in turn teach me things that help improve cryonics care. I also get economies of scale that drive down my costs in others areas. For instance, I now pay on $15.00 each for arterial filters, $70.00 for a 300 ft. roll of 3/8" x 3/32" bypass tubing, $25.00 each for cardiotomy reservoirs and $125.00 each for oxygenators. A year ago I was paying $60.00 for filters, $350 for tubing, and nearly $350 for oxygenators. (And no, I will NOT drop the rates I charge to clients (don't get your hopes up guys) because I intend to take the "profit" I make and plow it into brain cryopreservation research.) Animal research has allowed me to buy in bulk, buy nonsterile items and sterilize them and get help from manufacturers who want to see our work succeed because it means more product sales for them; several manufactuers are now selling me product at their materials costs because they believe in the work we are doing (and have seen the results). It also lets me keep staff trained and ready at way under the cost if I had to do so just to handle the occassional cryonics case. And the same is true of the profits (if any!) made from biomedical applications of our work: these too (not all but most) will go back into cryonics research. Finally, I question Bob's statement about the superior reliability of his stoirage dewars. Alcor, TT and others use high vacuum equipment. It is very reliable providing it is handled as high vacuum equipment must be: you must have it alarmed, check it daily, have backup dewars available. As far as I know everybody using high vacuum storage practices these standards. Having said that, I would still say that everybody would be better off adding perlite or other insulation as a backup to the vacuum because it is cheap and it will give added time to respond to any vacuum failure (a convenience). High vacuum equipment is only unreliable or less reliable than CI's units if you don't have or don't use the right resources to deal with failure. In CI's case, if the vaccum fails, removal of patients can be more leisurely. In EITHER case, proper facilities have to be in place to cope with failure. As long as Alcor has back-up dewars and adequate staffing, their approach is no more or less reliable. Perhaps less cost effective, but let's not bring reliability into it. And, as to cost effectiveness, this is still an open question as long as CI leaves unanswered the following questions (which I have asked many times before): 1) How much does it cost to fabricate the fiberglass units in terms of time, materials, etc. 2) Exactly what are the boil-off rates? 3) How much does LN2 cost? (Areas with high LN2 charges may be constrained to use very low boil-off containers). 4) What is the floor space cost to patient ratio? 5) What is the estimated working life of the unit? Then there are intangibles which are very hard to compare: ruggedness, burnability, portability, useful life (as opposed to the actual possible working life), and so on. Bob also notes that it will be ironic if CI's approach results in no cracking. This will be true only if it is the perfusion approach rather than the cooldown approach. I say this to gently remind everyone of the following: The cracking problem was uncovered by Alcor's work and that is credit which should be given. The initial response to the discovery of cracking was identical by both CI and Alcor: greatly slowed cooling rates between solidification and liquid nitrogen temperature. Mike Darwin Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=3088