Volume 5 no 39. First published June 1993. ISSN 0964-5659.
A Possible Cure for Alzheimer's Disease Douglas Skrecky
Are the Permafrost Patients Dead? Klaus Reinhard
Chronic Fatige Update Douglas Skrecky
Mathematical Life Extension Yvan Bozzonetti
Letters: Haloperidol, God, Creation of Evil, Cryonics, DNA Suspension, "Nanonics", Periastron, Veins
Coenzyme NADH: A Potential Life Extension Agent. Steven Gallant
What is Life Yvan Bozzonetti
Have it Your Way - Use a Trust Adolfo S. Pichardo
A Possible Cure for Alzheimer's Disease
by Douglas Skrecky
Alzheimer's disease is a type of senile dementia which is characterized by excessive deposition of neurotoxic beta-amyloid protein in the brain. Early onset Alzheimer's tends to run in families which possess abnormal gene sequences coding this protein.1 The specific initiating factor for this disease is unknown, but probably involves the increased generation of hydrogen peroxide, which occurs as brain mitochondria deteriorate with age. This hydrogen peroxide reacts with metal ions such as iron to produce highly destructive hydroxyl radicals. The simultaneous administration of the iron chelator desferrioxamine as well as extra iron to prevent an iron deficiency slows the progression of Alzheimer's by about 50%.2
Aluminum was once thought to be a factor in this dementia because some the earlier research had found evidence of increased aluminum in the brains of Alzheimer victims. This aluminum is now known to be due solely to laboratory contamination of tissue samples.3
A number of drugs besides desferrioxamine have shown some benefit to dementia patients, including tacrine, deprenyl and acetyl-carnitine.4, 5, 6 Vitamin E would probably be helpful as well, as it is known to protect against beta-amyloid neurotoxicity.7 However the blood/brain barrier limits the amount of vitamin E which can be absorbed from the circulation. Instead small amounts of coenzyme Q10 appear to be much more effective at protecting the brain by indirectly helping to recycle vitamin E. In a preliminary test daily supplementation with 60 mg coenzyme Q10, 150 mg of sodium ferrous citrate and 180 mg vitamin B6 eliminated virtually all signs of dementia in an Alzheimer patient. Progression of this disease was completely arrested for as long as the therapy continued.8
1 Mutation of the B-amyloid Precursor Protein in Familial Alzheimer's Disease Increases B-protein Production 672-674 Vol.360 1992 Nature
2 Intramuscular Desferrioxamine in Patients With Alzheimer's Disease 1304-1308 Vol.337 1991 The Lancet
3 Absence of Aluminium in Neuritic Plaque Cores in Alzheimer's Disease 65-68 Vol.360 1992 Nature
4 Editorial: Tacrine for Treating Alzheimer's Disease 2564-2565 Vol.268 No.18 1992 Journal of the American Medical Association
5 L-Deprenyl in Alzheimer's Disease 427-433 Vol.44 1987 Archive of General Psychiatry
6 Acetyl-Carnitine and Alzheimer's Disease 142-144 Vol.50 No.5 1992 Nutrition Reviews
7 Vitamin E Protects Nerve Cells From Amyloid B Protein Toxicity Vol.186 No.2 1992 Biochemical and Biophysical Research Communications
8 Coenzyme Q10, Iron and Vitamin B6 in Genetically Confirmed Alzheimer's Disease" 671 Vol.340 1992 The Lancet
Note This version is an updated form of one circulated privately before publication.
Are the Permafrost Patients Dead
by Klaus Reinhard
In Longevity Report 38 Douglas Skrecky in the article Permafrost Burial claimed that the two permafrost patients about whom he has received information, are dead. There are at least three permafrost patients, at least two from Europe. Both European patients are in hermetically sealed metal caskets. The first is in a zinc casket, the second in a stainless steel casket. In at least one of the European cases desiccation was taken into consideration but the mortician did not want to make a brain only treatment because he feared legal problems and the family did not want to make an expensive experiment with a whole body desiccation.1
Even if, in not desiccated permafrost patients, the recrystallization damage should sever all structures on the microscopic level, it is possible that enough biological information for repair remains on the molecular level. Think of a piece of paper in the macroscopic world: If you sever it, you can put the pieces together and no information is lost. The information is only lost if you burn or dissolve it. Bacteria in the Franklin expedition victims have survived 130 years frozen in permafrost. That does not mean that human cells will survive too, because the survival of a cell requires the survival of all relevant structures. But human cells as well as bacteria cells consist of proteins - lipids and nucleic acids. Therefore it is likely that some structures will survive also in human cells. That might be enough for a revival in the distant future because for nanotechnological repair only the information in the highly redundant biological systems is needed. Of course, if you can, you should improve your chances and make arrangements for better preservation and storage. But you should not use the word "dead" too early. In 1742 J. R. Winslow said: "The only satisfactory proof of death is putrefaction."
1 Remark for cryonicists who are interested in desiccation as back-up: No one can say whether dessication of the whole body by air drying or by using the freeze damaged cardiovascular system is possible. That has never been tested. However freeze drying or otherwise drying of brain-slices is possible with existing devices. The macroscopic damage created by cutting the brain into slices is probably negligible in relation to the freezing damage.
by Douglas Skrecky
The chronic fatigue syndrome has baffled scientists for years. Although it is usually initiated by a viral infection, no consistent signs of infection remain afterwards, despite there existing a persistent activation of the immune system. However the biochemical abnormalities which cause the feelings of fatigue may at last be close to being identified. Chronic fatigue patients have been found to have increased plasma levels of the norepinephrine metabolite MHPG and reductions in the serotonin metabolite 5-HIAA.1 As Sherlock Holmes would say "the game is afoot".
1 Plasma and Cerebrospinal Fluid Monoamine Metabolism in Patients With Chronic Fatigue Syndrome: Preliminary Findings 1065-1077 Vol. 32 1992 Biological Psychiatry
Mathematical Life Extension
by Yvan Bozzonetti
Who will pay for cryonics user's new life? If the technology comes to fruition in the next few decades, then the best answer may be: Make a capital investment in a form exempt from inflation and wait. Real estate looks good for no more than a fifty year period I think.
On a longer time scale, you cannot count on it: the East German example demonstrates amply why. If there is not a financially interested person or organisation to maintain the value of the "product", it starts to crumble after half a century. Its value reduces then to nearly nothing.
The simplest answer at this level may be some organisation such LIFEPACT, able to protect the interests of suspended people. All that is good for one or two centuries at most, if the technology lags beyond that, few human undertakings or organisations may survive, including LIFEPACT. The problem is then to "harden" the organisation.
There is one community in the world with tight links and very good record of duration and some power: The science establishment. From all the sciences, there is one with a particular status - mathematics. Maths is universal, it is used by all other scientists and beyond. It owes its power not from experiment or observations, but merely from internal consistency. It is a kind of art or purely human activity.
Maths has two faces: First an inner part, rooted in the brain of mathematicians and very difficult to grasp for others. This is mere thought in action. Second, a language made of signs and conventions. Each one needs to be learned to understand and use what has been developed by mathematicians.
Maths is more than a language: if you read (old) English, you can read Shakespeare. If you read Chinese, Lao Tseu is for you. Nevertheless, whatever you read you cannot gain the intellect of the author. Maths works in a different way: it produces ever and ever more condensed views of relations between elements and so finds a way to embody the intellect of the author. To speak in immortalist terms, this is a form of uploading. If you read Euler, you know Euler's writing and more - you have a part of Euler's brain power. If you are doing maths, every time you write about your finding in the field, you save a small part of your personality on the paper.
What to conclude? First, scientists must be a selected population naturally interested in longevity and cryonics. More so, there will be maths in the science training, and indeed there will be a declared interest on the subject. Contrary to expectation, biologists are not the best target for cryonics: Physicists are better, mathematicians look best. They already know a crude form of immortalism.
The second fact to see is the scientific tradition of care to others expressed by extensive reference to preceding works. No doubt: If there is a possibility to recover Euler someday, it will be attempted. This is not a cult of the oldsters; when you painstakingly learn a bit of mathematical theory and you see at the end the beauty it gives to understanding, you naturally want to meet the author of the work to exchange ideas and get more information.
Finally, there seems to be a small domain of mathematical theory with very profound links to physics: It is known as Moonshine - a three level joke. The domain is so vast in its implications than two people have a very low probability of getting to the same final topic even with the same start. Moonshine may be THE theory of the accessible Universe. If you start on the subject, no doubt, you will be a modern mind two or five centuries from now, with plenty of people interested in your subject. Nobody will bother about your recovery or retraining cost. Money will be not your limit.
From Mrs Joy Cass
I did enjoy (on page 10 of Longevity Report 37) the last paragraph of Mr M. Sankey's letter re "the inconsequential ramblings of Mrs Cass" etc etc for "in the way of such people" my inadvertent touching on an important point was probably deeply thought out and he didn't see that! His remarks re evangelism/survival are not separate interests - I find I need belief (ieevangelism) for survival.
[Paraphrased from three pages:] When one is a keen driver and has had a clean licence for 60 years, one is naturally rather fed-up when one is banned from driving as a result of being prescribed medication. A medicine, I may add, that reduces the patient to nearly total apathy! I cannot truly believe that such a drug can be of value other than the expediency of the wry desire of onlookers to shut up the voice and/or action of unwanted and awkward truths. Perhaps a resumé of the incidents that took place before the insistence on the part of doctors to maintain the patient's intake of Haloperidol will shed light and give reasons for these attitudes. ...[Here followed an essay about the usual city problems of abandoned cars, knocks on the door at night etc etc. - Mrs Cass lives with her husband in a flat in Hertfordshire, on the northern outskirts of London.] ... My reactions to Haloperidol are terrible irritation, ghastly leg pains and fearful inertia. ... My doctor reduced my dose to a quarter of a tablet twice a day.
I have looked up Haloperidol in MIMS. It is a medicine given to calm over active elderly people - which ties in with the remarks made by Mrs Cass. Tablets come in many different sizes, so one cannot ascertain how much a quarter of a tablet is.
I should imagine that Mrs Cass' doctor has offered or offered to arrange counselling as well as Haloperidol, and if so I would advise her to take it. Alternatively she could seek counselling with her church.
If the doctor is just giving out the drug with no counselling then I would have to agree with Mrs Cass' remarks about the drug being used to shut people up. However this is probably through sheer lack of time rather than any sinister political or religious motive.
I don't think that anyone would disagree with the problems of city life and a long term solution may be to move away from London, although of course I realise that family ties may preclude this option. Also it is sometimes unwise for elderly people to move from surrounding they know. However if these surroundings have become threatening, this factor could be negated.
The fact that I haven't published the details of incidents with cars and knocks on the door is merely because they may not be very interesting to other readers of Longevity Report. I think it is a good idea for Mrs Cass to write them down - writing itself is good therapy. It will also help her when she is discussing her fears with counsellors.
I read in MIMS that the action of Haloperidol may be achieved by "a central antidopaminergic activity". It seems that doctors don't know for sure how it works. The article goes on to say that it is of use in "management of organic syndromes such as dementia and brain damage". This seems to be in direct contrast to the use by life extenders of L-Dopa and Deprenyl to increase dopaminergic activity. Indeed, these drugs have been suggested for use in Alzheimer's disease, particularly the latter.
Obviously Mrs Cass should not cease to take the medicine as it has been prescribed by her doctor who must be aware of her needs and condition. Nevertheless the situation ought to be of interest to life extenders and possibly some of our readers can come up with some information on the action of Haloperidol and comments in general on its use.
Second letter from Mrs Cass
(Written after the above comment had been sent to her)
After talking to the specialist at the hospital for almost an hour, she saw my point willingly took me off Haloperidol there and then! Of course, I had put my foot down because I cannot go on with anything I do not believe. I then asked "Do you mean to say I can now this very afternoon go to my garage, get out my car and drive off?"
"Certainly," she said, "I don't wish to put clamps on your natural bright enquiring way. I merely want to help you and the best way I can do that is for me to have a word with your insurance agent and explain to him that only if and when necessary I can organise a minimal dose for you with no danger of your falling asleep at the wheel!"
Well, I mean, isn't that miraculous? I never expected that sort of cooperation. She trusts me, (as does my general practitioner) to dose myself when necessary. And to be honest enough to lay off activities if necessary. One does not abuse such trust.
Third letter from Mrs Cass:
A big thank you for the super Longevity Report 38. My thanks are grossly overdue owing to the deaths and terminal illnesses of the dear ones of my many friends and relatives. My writing time has been occupied in endeavouring to dole out comfort. In each case the people concerned were loved and greatly loving. And when the parting occurs (for the first time), especially unexpectedly, the shock can be quite devastating. My own personal experiences in the field of grief - as long ago as 1956 - gave me eventually the most surprising, and has time has proved, the most remarkable turn of attitude to death, from a one time fear to a miraculous welcoming of the beyond.
That is not to say I dislike life! Don't get me wrong on that. But if the inner man is not peaceful and trusting,1 the purely physical functions that for some are the total essence of living, can be such burdens and promoters of grumbling, self pity, that the memory of loveliness is blotted out. And what price then is experience? Failure and suffering are great teachers, provided one is prepared to seek deeper than mere face value.
As I write the Radio Four Daily Service is being broadcast and the splendid, spirited choir is rendering an enthusiastic Jerusalem2. Lovely it is. ...
Oh dear, this is almost becoming a sermon! What I really meant to say how interested I was yesterday in the two blessed hours I spent reading Douglas Skrecky's Extraterrestrial Intelligenceon paged 12-14 of Longevity Report 38. And, of course, your splendid editorial comment, with its lovely witty last line. ... His first paragraph is an expression of what people would describe as heaven. They hardly ever even consider its possibility of being Earthly. The U.S. government thinks it can be bought - by a radio search for evidence of Extra Terrestrial Intelligence. Mr Skrecky then asks three questions, and then proceeds to enlarge on this enormous subject, with its pros and cons and the enormous brain power employed on the project. The interesting analysis, and present information, with its possible outcome, so full of eternal questions made, for me, fascinating reading. It was beautifully put together, and certainly titillating. But who knows if they want the mystery unveiling? I think, if as he says our universe is still only a baby, let us as inhabitants of it try and learn the great lessons of happiness. They don't come easy, and basically are manifested by the experience of the opposite. The Fountain of Youth sounds lovely and silvery -but often such ideas degenerate into "showers" of the worst kind.
Is Youth such a wonderful state in which to be? I don't think so. I never did3. I longed to be 40 when I was 18. And could not unending happiness be the most awful bore?4 I take it that Mr Skrecky is relating his fountain of youth to homo sapiens? Well, these ideas are interesting to toy with.
But for my part I would opt for living my earthly life to its limit, in the faith of God's will; and looking forward to the future of the life of the spirit, as related to imaginatively by John on Patmos in his Book of Revelations. It is to my way of thinking the great free gift, and I wouldn't spend my few thousands on my corpse for the gamble of reanimation. Like the false start of our Grand National race recently, I couldn't begin my end so uncertainly! For to me it is the beginning of a change. There is no death! What seems so is transition. (Longfellow).
Your comment (Longevity Report 38 page 9) is so understanding to my point of view. But where, oh where are those Christians of which mention is made, who do not or will not speak about God?5 I've never heard so much nonsense. One only need to have Jesus' words to the woman at the well on that subject in order to be quite sure (John 4.24):
God is a spirit, and they that worship him must worship him in spirit and in truth. (Authorised version 1611).
The term Christian is a very loose one nowadays. But I am sure that one can tell those who really trust and love God by the way they study The Bible. It is a remarkable book, for its BC writings are as new and true today as when they were first recorded.
Let me give an instance from Isaiah, and before I quote let me acquaint you with his background. He came of noble family, he was married, and his wife was known as the prophetess. They had two sons. Isaiah's time was some 700 years BC. In chapter 45 of his book, verses 7,8, it states:
I form the light and create darkness: I make peace and create evil: I, the Lord do all these things. Drop down, ye heavens from above, and let the skies pour forth righteousness: let the Earth open, and let them bring forth salvation, and let righteousness spring up, together: I, the Lord, have created it.
I am sure some who read this for the first time will be astounded at the Lord's assertion of his creating evil. One must remember, however, creating and practising are two different things.6
Promises (vows) are statements of belief under which one is bound for ever. And his promise of salvation for obedient believers is the true motivation of a Christian.
When I used the word "Christian" to my father in the 1960s, he replied: "Don't kid yourself by using that word - all we can be is imperfect followers of Christ." to which I remarked "Touché." I think it is important for human understanding to realise how great is the temptation to go our own way. And because this sin is so irrestistable (we are, don't forget given free will) the trap is ever present, and we all fall in. Thank God we do, for then we have the chance to see how stupid we've been. And then we begin to see how little we see. And when that is made clear in our thinking processes we can be born again to understand the word salvation. The real goals of our being are surely the peace of mind which comes through our failures and trials endured in an apprenticeship of seeking the good.
The choice is ours, and as we are told by the psychiatrists "Its all in the mind." (A very true remark, for our thoughts and actions do go together.) Let us be warned, here and now, by that idea, as we've all been for ever warned throughout the whole written word of The Bible, as well as the examples of the lives of saints and sinners. Aren't we all a mix? Aren't we all in the image of God? Is not the whole thing a schizophrenic situation? Let us be humble and content to accept things that be7: and function happily within the time scale of our personal lives.
A challenge need not have adverse results if our basis is the will of God, and our desire to promote his reality.
Well, you see how stupidly I have behaved in writing as I have! Mr Sankey's (Longevity Report37, p 10) ... "the inconsequential ramblings of Mrs Joy Cass and in Longevity Report 38 page 8 "I do not object to Mrs Cass' Christianity, but to her muddled manner of expressing it." etc etc.
What an awful thing I've done - I have let a person of poetic ability see my words as "muddled ramblings". For, of course, other "Imperfect Followers" will be judged as being muddle headed too, would you believe it?
After I had read my given Bible passage early this morning, I read on at random and found the following in 2 Timothy 2.15 & 16
Study to show thyself approved unto God, a workman that needeth not to be ashamed, rightly dividing the word of truth. But shun profane and vain babblings: for they will increase unto more ungodliness. And their word will eat as doth a canker: of whom is Hymenaeus and Philetus.
It is worth reading on until verse 26 when the chapter ends.
But here and now I offer Mr Sankey an apology, for causing his objection. And I thank him for his sincere remark of truthfulness stating his feelings. Opinions are so valuable to all of us, for they are us! For everyone's sake, in every way, in every circumstance, we must put into practice the splendid word trio "Agree to Differ". (Understood, acted upon: result - peace and security, I reckon.)
I am most grateful for the interest Longevity Report gives me. And the pleasure of it for a silly old lady of 79 in October to be allowed to ramble on in its pages. She learns a lot. A lot that continually increases her faith. Especially when she is aware of generosity of vision and kindness of heart, in interesting editorial comments. A give and take of glad and joyful reading.
Thank God for eyesight and hindsight!8
1 Do we have any reason to be faithful and trusting? What is written down in The Bible is based on the thoughts of people in bygone ages. The human mind is capable of all types of thought, some based on reality and some on reality as we would like it. There is not a shred of hard evidence for a life after death. What we do have is evidence for people's longing for a continuation of life after death, and that is quite a different thing. Indeed there was a resurrection myth generated thousands of years before Christ, in the time of the Egyptian empire. Today, there are stories circulating that the singer Elvis Presley has risen from the dead. (This myth is discussed in the science fiction novel Elvissey by Jack Womak [Harper Collins 16, 319 pages]. I have not read it, but I have seen the review in the Financial Times.) A large number of people do believe in life after death, via many different religions. But unfortunately wishing does not make it so. The democratic process does not extend to manipulating matter by collective power of thought.
2. Yes, it is a great tune. The Nazis had great tunes for hymns of hate - indeed some still survive as hymn tunes in the Church of England (or maybe the National Socialists pinched them from that source, I don't know which came first.) Music is uplifting or depressing - it is a great mood controller. I don't know if anyone really understands how it can affect the mind as much as it does. Film producers know how to control the mood of their audiences by music.
3. Your refer to youthfulness of mind and body. Youth is wasted on the young. What immortalists propose is an old, ie experienced, mind in a young body, something quite different and something which has not been available up to now.
4. Rid of the ills of our present, we will be able to give more energy to exploring science and art. You seem to think that unending happiness is a sort of drugged stupor, perhaps with an inane grin on your face. This I agree would not be satisfactory. Immortalists don't see it this way. They see it is a path to self improvement, discovery and development beyond our wildest dreams.
5. I think he means that they are unwilling to discuss the fundamental issues of what the word "God" means.
6. I didn't know this point occurred anywhere else but in Genesis. It is, of course, the great problem of religion - if God created the whole universe and everything in it, then he also created evil. He also created all the diseases, including ageing. Yet The Bible tells us that this God is a loving God and is worth worshipping. One can only get around this contradiction by suggesting that one needs suffering, it is somehow ennobling. One can go round and round with this one, but if one steps aside and looks from without the circular arguments one cannot accept suffering as noble or anything else benevolent.
7. Immortalists have a word, or rather two words for that attitude - axe-kneeling! There are a number of small pictures of people meekly going to their execution because the state orders it that sometimes appear to make the point. (For example, see right.) If we really were content to accept things, then we wouldn't live in houses, wear clothes or even use tools.
8. And thank you for sharing your views with us. I don't think that either side will be converted to the other, that is not the point. The purpose is, as you say, that we agree to differ. Also it is that we understand what we are differing about. Some of the cryonicists will return to life. Indeed some younger people alive today may not even die of old age. However statistically they will die of personal accidents after about 600 years of life unless ability to restore mechanically damaged people is substantially improved. Maybe 600 years or so in the future the phenomenum of religion will be more clearly understood, most likely as a psychological quirk of humanity. But we must not close our minds to the possibility that a clearer understanding of physics may give a new boost to people's beliefs in what we at present regard as the supernatural. All religions have some grain of truth behind them, but this truth may be stranger than we can at present imagine.
From Mr Mike Zehse
According to Robert Shapiro, professor of Chemistry at NYU, one possible alternative to whole body or neuro cryonic suspension would be for people to leave behind a sample of blood, hair, or saliva to be preserved in the cold pending completion of the Human Genome Project.
Sequencing of DNA proceeds apace and Professor Shapiro suggests that by the year 2020 it will be possible to comprehensively map our individual DNA into texts which could be stored in a computer system at negligible cost.
For those who have the misfortune to be dead when science has made this breakthrough, their DNA texts could easily be retrieved from stored somatic material.
"Viewed from this perspective, a human being at death would resemble a play that had ended its run. No more performances would be given for a while but the script and stage directions would always be with us. When circumstances warranted, a revival might be staged."
Robert Shapiro The Human Blueprint: the Race to unlock the secrets of our genetic script.Cassell, UK 1992 16.99 ISBN 0-304-34226-2. [USA: ST Martin's Press, New York 1991]
I can't see how DNA samples would contain the memories and the learned (as opposed to genetic) part of the program inside people's brains. But thanks to Mike Zehse for pointing this book out to us.
A further letter from Mr Mike Zehse
Apropos Mel Gibson's new cryonic film Today newspaper ran a feature on Alcor UK to coincide with the film's opening. I think (but am not 100% sure) that was on Friday, 2 April. I heard the assistant editor of Today being interviewed on LBC radio and he adverted to Alcol (sic) and a Mr Sinclair who will freeze you for 75,000.
Space shuttle technology has recently arrived in this vicinity with ET-type green "wheelie bins" replacing the old galvanised variety and black plastic bags. Unfortunately, for technical reasons, this means a diminution in my paper supply.
From Mr Brian Blair-Giles
My Autobiography volume 5 is nearing completion. Composite with the previous four volumes, it will soon be published for 15. (Brian Blair-Giles Norbury Hall 55, Craignish Avenue Norbury London SW16 1RW)
I have given the name "Nanonics" to the application of Nanotechnology to the replicating, assembling and repairing of human cells, tissues, organs, and organisms, using particles length 10-9m, atoms, molecules and nanocomputers. I founded the first UK Cryonics Society in 1969, and now call it the "UK World Life Extension, Cryonics and Nanonics Society."
I shall be lecturing to the National Selected Morticians European Group Annual Conference on 21 June 1993 from 3.30 to 5 pm. The lecture will include details of the three major cryonics groups. Slides produced by Trans Time, Inc. will be shown, and the emphasis will be on the tasks that funeral directors can perform to aid the cryonic process. In addition details of funding research and individual reanimations will be discussed.
Editorial note -
We hope to publish a full report on the lecture in a later issue.
Periastron suggests caution onNanotechnology's role in revivals
Periastron for March 1993 starts with an article which expresses worries about the concept that nanotechnology is capable of restoring any damage done by present freezing methods. Because nanotechnology is not happening on any large scale practical level now, only theories exist. Theories are not constrained by the physical world, and therefore they can be dressed up by a sort of virtual reality into a world of wishful thinking.
The article goes on to talk about supramolecular chemistry, which is getting results now, and also mentions progress on Dr Donaldson's work in forming a scientific journal that will accept work from cryonics researchers. Unfortunately the journal has met with rejection from scientists outside of cryonics who were approached to join its editorial board. They say that they will be looking for funding, but not yet, and again there is no mention of whether they are looking for donations or investments. However the organisation is to be called The Institute for Neural Cryobiology and its journal will be Neurocryobiology.
The rest of the magazine contained some more on memory, and articles on laser controlled chemical reactions, and a piece entitled A Greek Drama.
This tells of how a woman dying of a brain tumour for which no approved treatment exists but who could benefit from an experimental treatment. Legal and political posturing between regulatory authorities is likely to delay treatment until the woman has died. Dr Donaldson wrote "I, particularly, wish the woman well, but I also suspect that she will probably be ground to death between the two wheels that mill around her."
The treatment involves inserting a gene for the system that stimulates the immune system into tumour cells taken from the patient and afterwards implanted. The gene stimulates the patient's immune system into a vigourous attack on the tumour. It has worked on animals, as yet it has not been tried in humans. Ultimately, such treatments could completely replace surgery for cancer, hence the aforementioned wrangling.
The primary source for this item is Science (259(1993) 452).
Periastron PO Box 2365, Sunnyvale, California 94087. Subscriptions cost $2.50 per issue. If you pay for many issues in advance, you avoid any possible price rises. If the newsletter does not continue for any reason, unused subscriptions will be refunded with interest!
One was an advertisement for a process known as Sclerotherapy, a non-surgical process from removing unsightly thread veins on the legs or face. For further details write to Transform, Lynwood, Green Walk, Bowdon, Cheshire WA14 2SN. I know nothing about this. If you are interested, then I suggest careful investigation before proceeding!
The other was details of a new surgical treatment for liver cancer. The Royal Liverpool University Hospital has become the world's first to offer surgery by supersonic water jet to remove cancerous tissue from the liver. The process cuts the tumour out leaving blood vessels intact and minimising bleeding. It is much safer than using conventional methods.
Only two other such instruments exist, but these are merely prototypes. One is at the University of Berne in Switzerland, and the other at the Sloane Kettering Memorial Hospital in New York.
A Potential Life Extension Agent.
by Steven Gallant
This brief report concentrates on the work carried our by Dr. Walter Birkmayer, the world renowned Parkinson's disease specialist, at his Institute in Vienna. Dr. Birkmayer published the first study on the long term use of deprenyl in Parkinson's patients in 1977. To my knowledge the work discussed here has not yet been confirmed by other researchers, however, it could be of importance to all those looking for safer drugs and possible new leads in the life extension field. The studies summarized below describe the therapeutic use of the natural coenzyme beta-nicotinamide adenine dinucleotide, reduced form disodium salt (NADH).
As readers of this journal will know therapies for certain diseases have particular implications for those interested in extending their functional lifespan. Parkinson's is of particular interest since many drug therapies are putative life extension agents, e.g. bromocriptine (Parlodel) selegiline (deprenyl) dihydroergocryptine, pergolide, lisuride and levodopa.
The biochemical cause of Parkinson's disease is a shortage of dopamine in the basal ganglia of the brain arising from a loss of dopaminergic neurons in the substantia nigra. The immediate precursor of dopamine, L-DOPA, was the first rational treatment for Parkinson's disease. This is still the mainstay of Parkinson's therapy, however, its limitations are widely known. It has been discovered that the L-DOPA producing enzyme tyrosine hydroxylase (TH) plays a central role in PD because its enzymatic activity is considerably reduced in the brains of these patients. The first indirect evidence for this enzyme defect was gained after patients were given alpha-methyl-p-tyrosine, an inhibitor of TH which caused the patients disability to deteriorate.1
In 1975 biochemical analysis of brain tissue revealed that the activity of TH is reduced in the substantia nigra of PD patients.2 Nevertheless L-DOPA remained the first choice of therapy either alone or in combination with inhibitors of DOPA-decarboxylase (carbidopa [Sinemet]) and monoamine oxidase (deprenyl). Unfortunately, L-DOPA does not work in a number of PD patients, in particular after long term treatment. New therapeutic strategies are needed. One possibility might be the stimulation of endogenous L-DOPA biosynthesis by activating TH. The TH enzyme is an iron containing enzyme with tetrahydrobiopterin (BH4) as coenzyme. BH4 was found to be reduced in the brain of PD patients by more than 50% thus giving rise to decreased TH activity. BH4 itself has been tried in clinical trials, however, the results were not very promising. This approach failed because the BH4 could not cross the blood-brain barrier. Oxygenase enzymes such as TH are often coupled with other redox systems. For TH it is the redox system NAD+ /NADH + H+ which restores the consumed coenzyme BH2 into the active BH4 form. This coenzyme is considerably reduced in the brain of PD patients. This may be because BH4 is not synthesised in sufficient amounts or is not activated enough into its reduced state. If the latter is the case, activation of the consumed oxidized BH2 should yield a higher TH activity and due to this and increased endogenous L-DOPA synthesis. With this in mind NADH has been tried in PD patients3.
All patients so far treated with NADH show reduced disability after only 4 days of therapy. The patients have ranged in age from 56 to 85, the duration of the disease in the range from 2 to 20 years. Over 60% exhibit a very good improvement of disability (better than 30%), over 30% a moderate response (up to 30%). In particular, the walking and pushing ability improved considerably and so did posture, speech and mimic.
The action of NADH has lasted between 1 and 2 days following a single dose, depending on the severity of the symptoms. After withdrawal of NADH from the usual medication a worsening of the patients disability is seen. This indicates the improvement of the symptoms is due to NADH. In addition to the improvement another effect of NADH is seen. Several patients have had improvement of their symptoms with NADH alone. In these cases the standard L-DOPA therapy is not needed. In all the other patients the L-DOPA dosage can be reduced up to 30% of the original dose. Some patients have been examined with regard to the duration of daily "on-" and "off-phases" because they were hospitalized and so easily available for observation. The daily on-phases could be increased in these patients in the range of 2 to 9 hours. The urine level of the dopamine metabolite homovanillic acid (HVA) has been determined before and 4 days after the beginning of NADH treatment . In all the patients examined a remarkable increase of the concentration of HVA in the urine has been found. Treatment with NADH appears to have the same effect as L-DOPA namely an increase of the urinary HVA concentrations. This would mean that NADH may substitute for L-DOPA. However, NADH is not a precursor of L-DOPA. It may be involved, therefore, only indirectly, in the endogenous L-DOPA biosynthesis . Support for this assumption comes from work carried out showing that cells of dopaminergic neurons, grown in the laboratory, produce more L-DOPA after adding NADH to the culture medium. Furthermore, TH activity was stimulated by NADH to 175%.
The clinical effect of NADH which closely resembles that of L-DOPA is also in line with this view. Indirect indications for the stimulation of endogenous L-DOPA biosynthesis may be derived from the increase in the urine level of HVA after NADH treatment which parallels the short-lasting clinical improvement. However, NADH is a coenzyme which can act on a great number of enzymes. Therefore, its beneficial effects in PD might include other enzymic reactions and its action may be a peripheral rather than a central one. This assumption is not far fetched since NADH has an extremely short half-life and it is "assumed" that it does not cross the blood-brain barrier. Additional studies are in progress to work-out the mechanism of action of NADH in order to gain a more rational basis for its anti-parkinson efficacy.
NADH and Depression.
Depression is a disorder which disturbs behaviour, physical and mental activity, emotional effectiveness and many other features which are essential for an active life with a balanced mood. A number of studies have revealed that certain neurotransmitters, in particular norepinephrine (noradrenaline), dopamine, serotonin and their metabolites play a role in depressive symptoms.
It has been observed that many PD patients suffer from depression. There are several reports on the improvement of depression after L-DOPA medication. When PD patients were treated with NADH it was observed that their depression disappeared. This observation prompted the testing of NADH on otherwise healthy people with depression.
For depression NADH therapy has been used for 2 weeks up to 12 weeks with an average treatment time of 5 weeks. Evaluation of clinical data so far indicates an average improvement of 80%. The improvement of individual patients has ranged from 63 to 96% of the original pre-therapy value. These findings indicate that NADH acts as a remarkably effective quick-acting antidepressant.
NADH has been administered intravenously, intramuscularly and orally. The daily dosage has ranged from 5mg to 12.5mg. PD patients have received 25mg daily or every other day depending on their response. The mode of application of NADH, parenterally or orally, does not give significant differences in the clinical effect. Therefore, oral administration via tablet/capsule is viable and certainly preferred by most users. A 63 to 96% improvement of the symptoms could be achieved with both forms of application. No side effects have been observed even after prolonged use.
NADH has been found to be of benefit to those suffering from all grades of depression. In order to determine the mechanism of NADH action we have to look at the biochemical events leading to depression. It has been claimed that the balance of neurotransmitters is disturbed and this change is responsible for the clinical symptoms of depression. One approach to treatment has been the use of monoamineoxidase (MAO-A) inhibitors, in order to block the metabolic breakdown of the neurotransmitters and thus achieve a higher endogenous concentration. MAO inhibitors such as imipramine and amitryptilin as antidepressants have been used for more than 30 years. One of the drawbacks of these MAO inhibitors is the blockage of the re-uptake of neurotransmitter from the presynaptic neuron. Therefore, the neurotransmitters accumulate in the synaptic cleft. This unnatural condition causes clinical side effects. The philosophy of using NADH as an antidepressive agent is its potential ability to stimulate the endogenous biosynthesis of L-DOPA, dopamine, norepinephrine and possibly other neurotransmitters. Previous studies have shown that there is a deficit in the brain of PD patients which seems to be responsible for at least some of the symptoms of depression. As dopamine is synthesized from tyrosine via L-DOPA under the action of TH, this particular enzyme is involved in depression.
NADH has the potential to counteract the declining levels of dopamine in "normally" aging individuals, i.e. older people with no overt disease in a similar manner to deprenyl. NADH has the further attraction of being an endogenous substance which could be used on a continuous basis without fear of side effects. Perhaps NADH may even be synergistic with deprenyl. NADH is also known to be a coenzyme for a wide variety of enzymes. If it can stimulate TH perhaps it stimulates others and could therefore have a generalised rejuvenating effect. Presently, the only drawback for NADH is its cost, i.e. around 10,000 per kilogram. However, if the therapeutic potential of NADH is confirmed subsequent bulk manufacture and/or improved manufacturing processes should bring the cost down to a more affordable level.
1 Birkmayer W (1969) Der Alpha-methyl-p-Tyrosin-Effekt bei extrapyramidalen Erkrankungen.81: 10. Wien Klin Wochenschr
2 Lloyd KG, Davidson L, Hornykiewicz O (1975) The neurochemistry of Parkinson's Disease: effect of L-DOPA therapy. 195: 453 J Pharmacol Exp Ther
3 Birmayer W, G.J.D. Birkmayer (1989) Nicotinamideadenine dinucleotide (NADH): The New Approach in the Therapy of Parkinson's Disease. 19(1): 38 Ann Clin Lab Sci
A full account of this work can be found in J. Neural Transm [P-D Sect] (1989) 1:297-302.
What is Life?
by Yvan Bozzonetti.
Up to the end of the preceding century and even beyond for some, life was a fundamental property, superimposed on matter and controlled and/or given by God. There was a vital essence or fluid. The pseudoscientific argument at the basis of that concept was somewhat as follows: All thermodynamic systems evolve towards thermalisation, disorder and energy degradation. Life, on the other side goes in the opposite way, it builds organized, more and more complex structures from simple materials. That is the proof of the "vital fluid action".
For scientists at the turn of the century, the counter argument was: thermal disorder growth is true for closed systems, life maintains itself as an organized system because there is a continuous input of energy coming from the outside. Eventually, the Sun is the energy source for every living being on Earth, throughout the photosynthesizing activity of plants.
Now there is a new twist in the theory. Thermodynamics studies the statistical properties of numerous similar objects, such atoms and molecules, in weak interactions. To apply thermodynamics to life is so to assume either a weak interaction between molecules inside cells and/or that strong interaction does not produce much more effect. The first assumption is false, nearly all chemical reactions in life systems do not take place in liquid solution where thermodynamics applies, they unfold on solid fibres or on membranes between compartments with different solubility properties. There can't simply be more nonlinear and strongly interacting systems.
In the past twenty years or so, strongly interacting systems with a small number of parts have been demonstrated to display a full rage of new behaviours, this is the domain of chaotic systems and fractal structures. To say than there is nothing more than classical thermodynamics is false from the start. Life is one step beyond our current theoretical capacities: it contains both, strong interactions and a large number of elements. What is certain, is that it can't be reduced to simple linear thermodynamics. Molecular biology give us an ever better understanding of the basic process and interaction of living systems, unfortunately, until we have a theory of large scale chaos there will be no understanding of complete living systems.
What are the implications of that for longevity and cryonics? The first seems to be a need to redefine the domain where we need to search for solutions. I give here two examples: nanotechnology and biology.
In the narrow sense, nanotechnology is the hope for mechanical devices, preferably self reproducing, to be able to repair molecular scale systems. In the top down approach, ever smaller classical systems are built, using the technology developed for electronic chip making. In the down up strategy, large molecules are produced and assembled by chemical interactions. Here, quantum mechanics, at least in its linearized form, introduces itself with molecular properties. The current debate seems to be: What is the best solution? My personal feeling is than both can produce good technologies, may be at different scales and with different aims and possibilities.
On the other hand, what really matters here is the answer to the question: can we hope to introduce a sufficient number of such devices in an extensively disturbed organism to bring it back to its normal function? Even if the devices are planned to act only at molecular level, in a nonlinear medium we can't suppress a set of effects at all scales. That is, a large number of nanomachines in an biological system (if they find room to work) will be certainly toxic at macroscopic level. The root of the problem lies in the basic assumption than life systems are made from independent, noninteracting parts, something as machines in a factory. The basic theoretical unexpressed idea assumes the validity of linear thermodynamics for living system. That 19th century idea is now demonstrated fully false. Surgery starts with the same idea, this is not to say it can't produce anything valuable. After all, graft technology save many lives every year; on the other hand, it is not, and will be never a general solution to damaged living systems. It is limited to the small domain where living behaviour may be linearized. Only slight defects can be treated in this way. Nanosystems will expand somewhat that domain but less than we can hope in a linear perception of the world.
At a fundamental level, biology reduces to biochemistry, this is the science of how complex molecules work and interact. Given a stretch of DNA, biochemistry learn us how to read it, how to get a RNA template, to edit it and produce the corresponding protein with its sugar tag to route it at the proper place in the cell or outside. This is an enormous achievement, culminating in giant projects as the human genome sequencing programme. On the other side, we are left without information about the macroscopic state of an organism, given its genetic makeup. Is it an insect? a mouse? a dinosaur? Taking the human genome, what happen if we displace a gene or a set of them from a place to another? Only experiment may give the answer today because we have no theory of complex strongly interacting systems at hand.
For simple systems, strong interaction produces a chaotic evolution. What is important to understand is this: chaos is not disorder and life is not pushed towards thermodynamics disorder but towards chaos. In fact, we live at the limit of chaos. To cancel disorder, we need to reverse time, cancelation of chaos asks only for inversion of some driving parameter.
If two differently coloured paints are poured in a cylinder put in rotation, the viscosity drag between the solid wall and the paint will put the liquid in rotation at different speed at different radii, at least during a transitory period. This will mix the two paints in a chaotic way, and no one at fist sight can tell if there is disorder or chaos. If now the cylinder is spun in the opposite direction, then antichaos is generated and paints becomes "unmixed". (are they?! - ed) For this simple nonlinear system, rotation is the leading time parameter of evolution. It can be reversed without bother about time control or reversal. On a very speculative ground, we may think about the driving parameter of life, something as the rotation of paint in its pot. A control of that parameter will give an hand on a living system evolution.
There is a more immediate concern: Can we mix the thermal (thermodynamic) strain imposed by cryonics with a nonlinear dominant parameter with a reverse analogue? If yes, then thermal effects of liquid nitrogen cooling may be superseded by the reversible added factor. What may be that factor? It will be a physical parameter imposed on the system, not a chemical cryoprotectant. Its inversion will put back the living system in its initial state, without use of nanotechnology. Well, there will be always the damage having produced the death state, to correct this, will be the domain of nanotechnology(ies).
On a practical ground, I'll bet on pressure generated at quantum level as the driving parameter. The energy stored by pressure in each molecule or even particle will largely overflow all thermal effect. The stored corpse may be then more disturbed than with thermal stress alone, on the other side, that disturbance is chaotic in nature and contains nearly no disorder. We can then reverse it. Mechanical pressure is technically unworkable at the needed level, magnetic pressure may seems better, at least for small samples. A better understanding of quantum system may be the key to a technologically sane solution. Whatever may be the final system, it will come from physics, not biochemistry or biology. This is the lesson we need to learn: Living problems are deeply concerned with fundamental physical questions, at least as much as with biochemistry. Unfortunately, our lack of understanding of nonlinear systems has heavily distorted our view towards the linear, chemical, part of the problem.
Who will work on the other components?
For further views of Mr Bozzonetti on chaos theory etc, see Fractal Report, available from us at 20/yr. Practical experiments for home computers are included. Introductory issue free.
Have it your way! - Use a trust
by Adolfo S. Pichardo, (Adolfo S. Pichardo Associates, Ltd.)*
The trust, simply stated, is a vehicle used for providing for the management and/or disposition of property. Once limited mostly to the wealthy, the trust is now used by all levels of society. The current popularity has evolved as a result of years of developing the knowledge of the trust's extreme flexibility. Its ability to adapt to change due to circumstances arising during its administration, together with the wide array of choices in stating its purpose, its beneficiaries and their rights, its trustees and their duties, all have led to the trust's development into a widely used vehicle for estate planning, business, tax savings, asset protection, and a multitude of other uses.
The creation of a trust takes place when legal title to real or personal property is transferred to a trustee. To become familiar with a trust and its benefits, one must first learn the meaning of the few terms used. For sake of simplicity, the most common terms are explained below.
Grantor The grantor is the person creating the trust by transferring property to the trustee.
Trustee The trustee is the person accepting legal title to the property, and the duties of the trustee as generally set forth in the trust document and/or by law.
Beneficiary The beneficiary is the person receiving either the income derived from the trust property (income beneficiary), the principal (remainderman), or both.
Principal The principal is the property transferred to the trustee to be held in trust.
The trust may be created during a person's lifetime (inter vivos trust) or by will (testamentary trust).
The property may be transferred to the trustee with a condition that may allow the property to be transferred back to the grantor (revocable trust), or it may be an unconditional transfer (irrevocable trust).
Depending on the intent of the grantor, the trust document may be drafted to:
A. allow additional contributions of principal,
B. be administered by a single trustee, co-trustees, and/or a professional trustee,
C. set forth the trustee's duties,
D. name an income beneficiary(ies), and/or remaindermen in any combination desired,
E. add or delete clauses that will defer, create or avoid taxation,
F. insulate trust assets from creditors,
G. provide for a smooth financial transition in the event of the grantor's incompetence,
H. prevent a creditor of the beneficiary from attaching the trust assets to satisfy the debts of the beneficiary,
I. ensure maximum privacy.
What makes the trust vehicle so valuable is its unequalled flexibility in providing for management and/or disposition of property. Needless to say that the above list of reasons for using trusts should by no means be considered all-inclusive.
In conclusion to this brief introduction to trusts, let us say that it is up to the legal counsel's creativity, when working with a specific client's individual needs, to draft a document that will accomplish that client's desires. Once the trust document has been created it is up to the interested persons to review the document at least annually to determine if there exists a need to change the document and communicate that need to the trustee and/or the legal counsel, as the case may be.
* Pichardo is a firm chartered by the State of Florida to provide professional fiduciary services. Their experience includes working with clients interested in the cryonic suspension process and their specific related needs.
3850 Galloway Road, Suite 306
Miami, Florida 33165
Editorial Note: this refers to US law, but if a UK resident were to set up a trust in the US, then it would be under US jurisdiction.
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