X-Message-Number: 5020 Date: 20 Oct 95 18:33:59 EDT From: Mike Darwin <> Subject: CRYONICS:response to Merel and Donaldson Peter Merel writes: >I'm afraid I've misplaced the reference, but as I understand it CryoCare >is intending to sample a few microlitres of neurons from each suspendee >in order to evaluate and improve its suspension procedures. This is true. And it is due to a decision by me (BPI) to make such sampling a requirement for all patients I treat. >While I'm yet to sign up (yeah, yeah, bite me) I've been thinking that CC >are probably the mob for me, so I gave this a little thought. Although >I appreciate the need to evaluate these procedures, I'm worried on three >counts: >. the samples, if always taken from the same spot, may not be representative >of the quality of the procedures with regard to the whole brain. >. if samples are taken from random spots, it might be that one of the spots >contains information that is difficult to interpolate, especially if the >technology used to reanimate the suspendee is less potent than nanotech. *I assure you that the sample(s) I plan to take, (and I am now considering taking SEVERAL) will not necessarily be representative. But so what? It IS the cortex I am talking about here. The condition of the cortex, particularly the more senitive (injury wise) frontal cortex is actually representative of the worst case injury. * Good results here will be very meanigful if they hold up statistically. * Bad results, while not necessarily accurately reflecting the overal condition or prognosis for a given patient or class of patients, may (likely even) tell us about WHAT the reason(s) for the "bad" results might be. We can get a lot of data these days out of a wee bit of tissue. * Some feedback is better than none. What we have right now is a black box. The problem with most of you guys is that you envision your death with the cryonics team right next to you as you waft gently off into tomorrow, like some movie hero or heroine saying deep or emotional thoughts until their head gently lolls to one side and they have "died." This is NOT reality. Even many optimum patients have horrible precryopreservation problems: prolonged hypoperfusion with possible failed cerebral perfusion hours before legal death, elevated intracranial pressure due to tumor, death from acute stroke and all its effects, AIDS encephalopathy, and on and on. I have no idea what I am "starting with" after transport on ANYBODY. And human brains or bodies collected under other circumstances will tell me little about the population of patients I am actually working with. Right now one of my patients is sitting in hospital here who thought he was doing quite well on his alternative therapy for cancer. Steve Harris, M.D. and the rest of the BPI assessment team went out and saw him on Sunday last. Steve found clinical evidence of a brain tumor in the occiptal lobe of the brain. I told the family the tumor was likely somewhere between the size of a walnut and a golfball (quietly I said to myself and later to Steve, more likely the size of lemon). The patient was CT'd two days ago: 6 cm metastatic mass found in his occiptal lobe. Last night he was rushed to the hospital with other complications which may (or more probably are NOT) related to his brain met. Many patients I've done under "good conditions" like Arlene Fried and Dick Jones had either brain mets or other space occupying lesions (toxoplasmosis in Dick's case). In both the case I have now, and in Arlene's case, palliative radiotherapy will be given and is essential to manage the patient both medically and cryonically. (Even non cryonicists don't want to be paralyzed on one side, aphasic, incontinent, impotent and/or demented months before they die). Believe me, the radiation this fellow is going to get and the radiation Arlene got is going to do more damage than ANYTHING I do with a biopsy! Further, collecting this material will provide not only quality control but vitally needed feedback to advise patients of what course to take. If I see consistent autolytic changes in brain biopsy samples taken from people who die of high intracranial pressure (with possibly hours of failed cortical perfusion at 37 C before legal death is pronounced) then discussing appropriately timed death from voluntary dehydration would definitely be an option for discussion with the patient. Ditto cases of prolonged shock where there are perfectly ethical and legal maneuvers to hasten legal death such as sitting them up in bed, bathing them, turning them, etc. that are routinely used by hospice to speed passage through a dragged-out agonal phase and spare the family the horror of watching someone they love die this way. Ditto stopping palliative O2 supplementation in obtunded or comatose patients who are not getting good brain perfusion. O2 in such cases drags out the dying process and is actually medically inappropriate; however without hard data many people in cryonics instinctively feel it is helping the brain and are loathe to stop it once its palliative value of combatting air hunger in a conscious patient is long gone. We ALL need this data. Further, the notions raised by Donaldson, Merel and others that this is likely to cause some kind of loss of memory or a clinically significant problem now (i.e., if done on a healthy living patienttoday) is absurd, especially in the context of the typical cryonics scenario before freezing, let alone AFTER freezing!!!!!!! Leaving aside the issues of infection, anesthesia related complications, subarachnoid bleeding and so on, associated with brain biopsy on LIVING people, I would not hesitate to have such a biopsy done myself tomorrow. Since NONE of these factors applies in cryonics cases (the head is already opened, the dura is open, the bridging veins are torn and fluid is leaking out of the burr holes...) the only issue is loss of "vital information." I've seen dozens of brain biopsies done in my day and, performed competently, they don't do a damn thing to hurt the patient's cognitive or memory performance. As I pointed out to the family of the patient with the colon cancer: I know this tumor has to be this big because a tumor in that area much smaller would not be evident clinically. Indeed, even a tumor the size of a marble is not evident by any psychological testing or neuro exam in some areas of the brain. They are only found on CT, often with the CT being done for unrelated reasons. Here this patient is sitting there having dinner with us and carrying on complex conversation and neither he nor his family had any idea he had a 6 cm mass in his brain! Give me a break! BPI plans to use the nondominant hemisphere and we have two consulting neurologists who will be determining the protocol and sampling sites on the cortical surface. If Donalson and others want to go screaming into the night over medical-quantity and quality biopsies, so be it. If most CC members don't want this done they can say so and BPI will not touch the case; they can go to Alcor or CI and I feel sure that CC would actively seek to contract with Alcor or CI for these patients' perfusion and ante and post arrest care. I have the perfect right to practice in a way I choose and in a way I feel best for both the patient, cryonics, and so on. Similarly, the patient has the perfect right to say 'No way, Jose, I'm outta here!" Could be I'll have only a few people signed up for BPI services. So be it. Could be I'll be out of the cryonics business completely. So be it. (And wouldn't that make some folks happy campers?) I think this would be a tragedy (but then I can hardly be objective!). But, the world is full of tragedies, and not getting information to help the patient and others is tragic too. Further, the Anatomical Gift Act specifies that such gifts are for the purpose of teaching and research. Cryonics, which uses this law, as practiced by most groups, are doing neither in any kind of definitive or scientifically defesible way vis a vis the actual patients they get and cryopreserve. >. in general, the procedure seems to go against that "first, do no harm" >bit that doctors are so nutty about. Actually, that line has (to my great dismay) been dropped from the standard medical oath and in most countries outside the US and is no longer considered "meanigful." This is fresh in my mind because I just had a net discussion with several physicians (and 500+ nonparticipant "lurkers') over just this issue. They think it passe. I don't. But, "first do no harm" must be taken in the context of its meaning. It is a very deep statement with profound implications and subtelties. Clearly if you have a brain tumor which will kill you, getting 5K or so rads of radiation to your forebrain is not going to do your brain no harm! But, then, neither is a tumor! Look at Donaldson: he had heavy duty radiotherapy for his tumor and he is still alive and doing well. It's a damn good bet he'd be long dead if he had left it untreated. Yes, he has suffered side effects or harm from the radiation including acute things like profound fatigue in the weeks/months following the treatment. I think he also would state that he has suffered modest cognitive losses as a result of treatment. Finally, I think he would say that it was a good decision despite these things! If you have a blown appendix the surgeon has to harm you by cutting into you. That is obvious and well worth the risk. So, implicit in do no harm is to use only treatments that can reasonably be expected to improve the patient's lot as opposed to making it worse. But the dictum runs deeper. It says, you must strive for treatments that progressively optimise outcome while minimizing "harm" or side effects. So, today, we remove gallbladders with tools poked through small holes in the belly instead of cutting a 12 inch gash in the patient's body wall with accompanying high mortality, extreme pain, and high morbidity (average hospital stay in my day was 2 weeks, average with laproscopic cholesystecomy today is 12-24 hours). My duty is to every patient. Certainly it is first to the individual patient and second to others. But, BOTH must be considered. As long as I inform my patients of how I am splitting things up and get their informed consent, there is no problem. In fact, I believe that existing CI, CC, and Alcor paperwork already contain the necessary language. I don't have a copy at hand, but I think I "stole" the language from CI which (from memory) says something like: "Further, I consent to the removal of nonvital portions of my corpus (body) for investigation and testing the purpose of which is improving and pefecting the science of human cryostasis, cryonic suspension, etc." Clinical-type brain biopsies conducted on the nondominant hemisphere (this will not be possible to absolutely determine, particularly in the case of left handed people who typically have more of a spread of functions over both hemispheres) in nonvital areas (i.e., no detectable change of intellectual performance and mentation) are more than justified in my opinion in the setting we are working in, and constitute a reasonable balance between "harm" and "help." >Now I don't know if it is practical or ethical, but another way to do this >testing occurred to me. I know that it wouldn't be possible to get access >to the bodies of people who haven't signed an agreement with CC - even if >they'd signed up for organ donation it's unlikely that the authorities >would see cryonics research as a valid purpose at the present time - but >it occurs to me that there might be a another source of fresh human bodies. If there is I'd love to know about it. However, even the freshest available for medical research are at least 2-4 hours old (with rare exception) and further are very costly. Further still, they will have little overlap with cases where "CPR" and perfusion are begun within minutes of death. >What I'm thinking is that there are a lot of people who die in jail. >Not people who are executed, but people who get into knife fights and >so on. People in jail are often very poor, desperate and short sighted >- ie. they'd be willing to sign an agreement in exchange for not much >money. The agreement here would be that upon their death their bodies >would be donated to CC. I daresay that arrangements could be made with >prison authorities and doctors to make sure that appropriate cooldown >procedures were followed, so experimental conditions could be very well >controlled. To the best of my knowledge in most states (including California) all executed persons are autopsied. Further, I am reasonably confident that in ALL states deaths while in prison or under sentence are always autopsied (for obvious reasons!). I understand, for instance, that Jeffery Dahmer's brain was retained after the post and is still in fixative (source= Jay Leno). >Somehow a lot of my ideas in this arena turn out to sound pretty ghoulish, >and this one is certainly no exception, so if you're easily shocked read >no further. >If this could be done, then CC would have a ready (steady?) source of >human experimental subjects whose brains could be sectioned and >examined in their entirety. There are only two risks I can see in >this: first, it's one of those arrangements that the tabloids would >just love to report, and second you could get the bodies mixed up ... Ghoulish? On this list? Surely you jest! Impractical? Could well be, but never ghoulish. Finally, you can look at this issue at least two ways. On the one hand, other cryonics groups can say: "My God, don't let that Darwin fellow get a hold of you, he'll be taking teaspoon's full of your brain out to satisfy his Mengle-like curiosity! We don't do that here!" Then there is the other way: Darwin will sooner or later have books full of case reports and EM data (and possibly biochemical data as well) documenting how patients in different circumstances look after transport and/or perfusion. He will be able to "show his work" and it's a good bet his work will get better. Every time in my career that I "looked" at patients using a new modality it has resulted in vast growth of knowledge and improved care. Fior years people just packed patients in bags of ice after they died with the result for most being that 6-8 hours later their core temperature was still at or near room temperature. The portable ice bath which simulates the cold water drowing Bob likes to refer to so much came out of my plotting the data that had been collected. I was apalled at what I saw! (Nothing like graphics for making raw data meanigful!) Refinement by Fred Chamberlain with introduction of convective stirring resulting in almost the same magnitude of improvement in cooling. In short, the time to reach 15 C with external cooling is about 1/4th that or better than with ice bags. You get what you pay for, and the coin of the realm isn't always money. I am willing to listen to reasonable arguments as to why this course of action is a bad idea. However, ask Brian Wowk to show you MRIs of the AVERAGE 75 year old's brain. Better still of the average 85 year old's brain. I have two tacked up on the filing cabinet next to my desk as reminders of what ahead (no pun intended). Further, go talk to a neurosugeon or neurologist about the impact on memtation of brain biopsy (excluding all complicationswhich do not apply or aleady present in patients treated using the "ideal" approach BPI and Alcor currently use). Mike Darwin Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=5020