X-Message-Number: 99 From: Brown/Donaldson Date: Jun 25 1989 Subject: Memory Mechanisms & Ischemic Damage I have appended below two questions concerning memory mechanisms and ischemic damage, both of which are issues of importance to cryonicists. Following that I have appended (with his permission) Thomas Donaldson's reply. - Kevin Q. Brown ...att!ho4cad!kqb Thomas, . . . I also have a question for you concerning the molecular mechanisms of memory and loss of memory from ischemia. The paper "Biochemistry of Information Storage in the Nervous System" by Ira B. Black, et al. (June 5, 1987, Science, Vol. 236, pp. 1263-8) suggests that long-term memory involves alteration of gene expression (rather than just changes in the synapses). Also, the note "NMDA Receptors Trigger Excitement" by Deborah M. Barnes ( Jan. 15, 1988, Science, Vol. 239) suggests that ischemia leads to destruction of the cell via excess production of protein- and fat-digesting enzymes. Assuming that these articles are well-regarded in their fields and my interpretation of them is correct, do these articles help provide answers to the following? (1) How long does it take those enzymes to destroy the nucleus of the cell (where the DNA and, presumably, much of memory are stored)? (2) How soon after deanimation must a cryonics emergency support team reach a patient? Thanks. - Kevin Q. Brown From arpa!A.ISI.EDU!TKD Wed Jun 21 08:52:35 EDT 1989 Date: Wed 21 Jun 89 08:52:35-EDT From: Thomas Donaldson <> Subject: Re: memory mechanisms and ischemic damage To: In-Reply-To: Message from "" of Tue 20 Jun 89 22:46:32-EDT Message-ID: <> Hi Kevin: I wrote up a reply to your two questions. After some searching, I did find the "protein and fat digesting enzymes" phrase. Current thinking about brain damage is that it comes from loss of ATP first of all. I cannot recall any paper suggesting such a process occurs in brains (remember the NMDA seizure is now well studied). I will go so far as to suggest that it is a misquote by the reporter (as you know, those columns are written by reporters, not scientists. NATURE has all its reports done by experts in the area studied and reported. Rah for NATURE). Here is a further answer: Kevin: While we don't know answers to your questions (rocksolid KNOW) we're awfully close. I have just sent off a report to CRYONICS about two papers (PG Nelson et al SCIENCE 244 (1989) 585-587 and ER Kandel et al NATURE 339 (1989) 51-54) which come close to telling us how neurons/brains store memory in their structure and chemistry. I remember the Ira Blacks paper clearly because it was one of the first to raise the issue of memory storage in the nucleus (locks on the DNA just like in development). Unfortunately so far we haven't QUITE identified these chemicals if they exist. Perhaps some other process is involved. My guess is that some kind of nuclear mechanism is involved. Memory is too durable to be retained permanently other ways. Cells are more like tornados than machines: they are constantly turning over and rebuilding themselves, very little constant. The DNA is one of the few chemicals which does not. (I'll refrain here from an advertisement for cells/bacteria rather than more "mechanical" nanotechnology). As for your second question, you need not worry at all. The article is referring to a kind of "chemical seizure" which overtakes all neurons at once just AFTER ischemia ends and circulation is restored. It's very widely studied now. They all try to fire off at once, repeatedly. The process does seriously deplete their stores of readily available energy: that's why they can't normally recover by themselves (among other important reasons, but that's shaping up to be a major one). The process provides no danger to any other part of the cell, in itself. Once we discover the chemistry of memory, survival of those specific chemicals plus indications about structure (cf the papers and notice I said "indications") will be necessary and sufficient to answer your question about survival. We don't quite have that. One fascinating point about nuclear storage, of course, is that it's likely to be far more durable than we had ever expected. We can recover intact DNA from cells well into the rotting process! But nobody now can promise a thing now). ------- Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=99