81 replies to this topic

[arun]

Aloha,
(Being a very new member, i'm not sure about posting etiquitte. ) Reading
Bruce Klein's essay, "Why Physical Immortality", I was very pleased to see some credit given to the late Alan Harrington. My reading of his book, "The Immortalist" was a mile stone in my philosophical life. This book is rather difficult to find and I'm fortunate to have somewhere a signed copy now in hard cover.

My question for folks is how do i maintain joy in life now when thoughts of death are with me so often. I fear immortality is not going to happen in time for me. Where does an atheist, transhumanist find solace?

Thank you all for maintaining this internet group.

Live long and joyously prosper,
"Arun" (I get email presently best at arundinatwo@aol.com)

[Bruce Klein]

Where does an atheist, transhumanist find solace?

Welcome, arun. While looked at more of as a backup plan than a solace, cryonics may be a good option for an atheist.

[Mind]

Arun, perhaps you are at an advanced age. Still, every step you take to exercise and maintain a healthy diet will add some time to your clock. You may want to investigate anti-aging supplements. As extra insurance, check out cryonics. Good luck and feel free to ask questions here in the forums.

[sosnovin]

Thanks.
It is nice.

Sosnovi

[Bruce Klein]

You're welcome, Sosnovin.

[johnbellceo]

Greetings and it is nice to come back again and read about one of my primary interest - longevity and immortality. Our company will in time be doing some research in this field and also providing tools to researchers to help them. Cynthia K.s work on the insulin gene is fascinating and I think she is truly on the the trail of one serious approach to reversing aging. I am an author of an upcoming book on Reversing the Aging process and it is an honor to be here among some of the most innovative and visionary minds on the planet.

jb

[thekingsfool]

i do admit, i find immortality to be quite intriguing, and you have brought up some strong points that apeal on an intellectual level that almost reaches the romantic (to stop the great losses of knowledge that occur each and every time another falls under deaths scythe -in a manner of speaking), but there are odvious problems with immortality, not in the acheivement, persay, but in the practice (so to speak).
Odviously everyone could not be immortal, that would cause a great number of problems (not only from a social stand point...), but then, if not everyone can be immortal, who can? and if a person is deemed worthy of immortality, what criteria was used to make that decision? who will be allowed to make that decision? the list goes on. these questions can be asked of most anything that the human mind can conceive. sadly, most ideas such as this are beautiful when in our heads, but beastly when they take a more tangible form.

[champion]

Why Physical Immortality?

Physical immortality can be whatever you perceive it to be.
Your perception of what physical Immortality means, has influence on the emotions and idea's it conjures up.

I think enough people can focus on the negatives, and that creates fear which there is too much of as it is.

I think when we talk about Immortality, I would infer that a factor in whether they perceive it is a benefit or a negative comes from how we ask the questions, and the state of being or quality of life associated with it.

Immortality looked from the eyes of love, warmth, understanding, creativity, compassion for fellow man, could be the greatest gift.

All our emotions are states of being, and we tend to influence them by choosing what we focus on. Ie. Focusing on gratitude and thankfulness for all the things you have creates the Emotion of gratitude. We condition our minds to even think in patterns throught repetition of the syntax of questions.

It's like our perceptual world is this big (- - - - - - - - - - - -) and we barely see a fraction of it ( - ). But what we choose to look at or focus on, and the way we interpret it has effects on our nervous system, and thus the emotions we feel.

I think human beings are capable of anything they can imagine, even Immortality, or life extention, symbiosis with machines, an here's why.

When people get passionate about somthing, I mean they really feel it and believe it in their being, it is a physiological state where the most difficult thing become easy.

What's the point of Immortality if it's spent in the right physical and physiological state?

An let's say that we do have a level of control over our mind and body, then what? How do we realize our dream of Immortality?

I'll simplify it to two things.
1. We need to learn and understand the body's mechanisms in order to figure out to give it the greatest span of years. This might include the environments we surround ourselves in, the food we eat, suppliments and drugs that might assist us, and manage our states of mind to which ones promote longevity. We also need to be clear on what we are defining as Aging and how to slow it down or prevent it... is aging cellular degeneration, cumulative organ damage, ext.

Giving us the greatest span of years might allow us to live long enought to be there when new technologies and understandings are reached.

2. If you feel you have the ability to contribute to the research and understanding of such a cause, then do so.


- and at the end of the day, it's all about balance. That our dreams of Immortality may not be reached, that it is an idea, that is possible but somthing might thwart it - at the very least we need to make sure we get the most out of each moment and leave behind all the love, passion and great things we wish for the future.

Death's gonna take a long vacation, through persistance and understanding we'll find ways to maintain the energies know as our consciousness, or our life indefinately. We'll make the world a thing of dreams.

- Champion J

[dougatfad]

Bruce said:
"We debated the term ‘immortality’ extensively beforehand, yet came to the conclusion that ‘immortality’ was right because it sets the right tone.

There may be initial misunderstandings because of the association with a spiritual and religious immortality, but this is quickly overcome by our evident focus on science.

The reason why we chose ‘immortality’ as opposed to more conservative terms, such as ‘life extension’, was that we don’t want to limit ourselves by any implied ambiguity. Even though we’re unable to live forever at this point in history. we believe this problem can be overcome."


From this I'm assuming one of two things: you're actually talking about physical immortality, ie: remaining in the body you now have, forever. Or you're talking about some kind of scientific immortality. If the latter, what does it actually mean, and if the former, what's stopping you from being physically immortal now?

Casanova said:

"I have found that it is religious questions that begin, continue, and make exciting, the search for answers."

I have no way of knowing whether that statement is true. My experience of people of faith, whatever it might be, is that when you start a search from the viewpoint of a particular set of beliefs, the answers that are acceptable are automatically predicated by the limits of those beliefs.

To pursue an unlimited search, you have to start with an unlimited desire, regardless of how unrealizable that desire may appear to be.

Casanova also said: "For me, one of the questions is, "how did God do it." The design questions are fascinating."

Straight away you have limited the answer. By assuming God you have excluded any other possiblity - that hardly makes for an exciting or exhaustive search. And in a sense it wastes time with something that's irrelevant. How we came to be, or even why we came to be for that matter, are one of the main distractions from exploring who we are now and how we can be in the future - not as some scientifically enhanced being but simply as the flesh that we are. I don't deny that we are extraordinary, but it's not the mechanics of how we work that's most fascinating, it's the way we are always looking outside ourselves to validate our existence and attempting to manufacture a division between who we are - our mind, spirit, soul if you like - and what we are - our flesh. There is no division, we are all of it, one part cannot exist without the rest - you may believe it does but there's no evidence scientific or otherwise to support that view. And it's that view - of a divided being - that makes the human life so dispensable. Until we recognize the completeness of each individual, there will never be a coming together - we have to end the split in ourselves before we can end the split from each other. Ironically, the way to end the split in ourselves is to end the split from each other - which is not a catch 22: it just means we have to do them concurrently.

God is the lazyman's answer to the unkown. Of course, to be alive, physically immortal and joyful you don't need all the answers, nor are you threatened by what you can't explain. I don't need all the answers to live and I certainly don't need to buy into the invention of God (which by the way is still an unproven theory) to make me feel comfortable about what I don't know. I have people whom I can touch, feel, and communicate with (which is what makes life worth living anyway), and it makes just as much sense to me that we (human beings that is) created everything, as to believe that a god did. Neither theory can be proved, but we're here, god's not. And there's no indication that we can't have created everything. Every progression and regression we know the history of so far has been created by people - only a lack of self worth leads us to believe we are limited.

[Bruce Klein]

From this I'm assuming one of two things: you're actually talking about physical immortality, ie: remaining in the body you now have, forever. Or you're talking about some kind of scientific immortality. If the latter, what does it actually mean, and if the former, what's stopping you from being physically immortal now?

The latter, but with the option to enhance our bodies for durability.

Misguided perceptions on aging and death hinder our progress toward physical immortality. Aging is not inevitable. Aging is a curable disease.

My personal opinion is that death equals oblivion.

[rachel41]

I look forward to physical immortality; if it means being able to prevent mistakes of the past and help provide a better future for society.

Despite suffering with SP( spastic paraplegia); I would love to live like Methusaleh, so that I could help others around the globe.

I have an interest in microbiology and science and already sharing my knowledge with my neighbour's grandson. Imagine living for 1000+ years and all the knowledge that could be shared.

We could improve our environment and our ecology and we wouldn't have to reproduce like we do now to proprigate our species.

Our cultures around the world would have to stop making war for it to really work.

All things are possible and I would love to be able to live a thousand years. The other problem would be youthfulness. It is no good being a thousand+ years and not be physically fit and healthy. My condition is a drain on the benefits system now, so being a pensioner, or disabled would make me a liability in my current condition.

So not only do we have to slow down ageing; but find ways to regenerate nerve and muscle tissues.

love, light and peace

[Infernity]

I look forward to physical immortality

Of course Rachel, without it "you" wouldn't be able to look forward at all...

Yours
~Infernity

[John Schloendorn]

No worries, Rachel, indefinite health is the most promising way to achieve indefinite life... Most human deaths are caused by frailty that's why frailty has to end. So youthfullness is not the "other" problem, but really they are only one. You will find that much of the discussion about ending death on this site is actually about ending frailty as a first step. Good news, isn't it?

Btw, Tissue regeneration is indeed very promising and incidentially I'm preparing to start a PhD project in this area soon.

Good to have you here.
John.

[danpop77]

Winning The Battle Against HIV-1: (MPTV-x , HAART-x) / (MPTV-x , Mega-HAART-x) - Couples Formed of a Multivalent-Polivalent-Therapeutic-Vaccine (MPTV-x) and Its Corresponding HAART-x , or Mega-HAART- Regimen , Respectively.


Iosif Secasan
Department of Urologic Surgery
Spitalul Judetean Resita / The Hospital of Resita
RO-1700, Resita , Romania

Dan I. Pop
Data International SRL
Str. Horia, Nr.6, Bl.6, Et.10, Ap.39, Resita-1700, RO-1700, Romania
Phone: 0040-722-940299 , E-mail : danpop77@yahoo.com

Ciprian C. Secasan
Department of Microbiology / Department of Urologic Surgery
Spitalul Judetean Resita / The Hospital of Resita
RO-1700, Resita , Romania



Abstract : This article presents an entirely new theory and practical solution to eradicate HIV-1, based on HIV-1's ability and need to mutate under HAART-x / Mega-HAART-x drugs pressure, and on the sinergetical scissoring effect on HIV-1 of
(MPTV -x , HAART-x) - couples and (MPTV-x , Mega-HAART-x)-couples, which are formed of :
1. a multivalent-polyvalent-therapeutic-vaccine (MPTV -x) , made of whole-killed HIV-1 (or of particular parts of HIV-1) bearing on its genome (biochemical structure) the resistance-mutations-pattern (RMP-x) that would be induced by the following , to come HAART-x or Mega-HAART-x regimen and of
2. the respective, corresponding HAART-x or Mega-HAART-x regimen, respectively.


Key Words :
HAART (highly-active-anti-retroviral-therapy), HAART-x regimen, Mega-HAART-x regimen, point-mutations (PM),
resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x), resistance-mutations-pattern (RMP-x-),
multivalent-polyvalent-therapeutic-vaccine (MPTV -x), (MPTV -x, HAART-x)-couples,
(MPTV-x,Mega-HAART-x)-couples, drug-resistant-virus(DRV) , drug-sensitive-virus (DSV);



Introduction

Time has come for Science and Medicine to win the battle against HIV and AIDS.
Since a classical vaccine against HIV-1 is hard to design or even define, and since current HAART (highly-active-anti-retroviral-therapy) and even Mega-HAART regimens are unable to clear an HIV-1 infection , a combined and coordinated strategy has to be adopted, in order to achieve HIV-1 eradication.


(MPTV -x, HAART-x)-couples followed by (MPTV-x,Mega-HAART-x)-couples

This article presents an entirely new theory and practical solution to eradicate the HIV-1 virus from the body of any HIV-1 infected person, by combining HAART (or Mega-HAART) with a multivalent-polivalent -therapeutic-vaccine (MPTV), pre-administrated to HAART, (or Mega-HAART respectively) , and targeted against the in-advance-known resistance-mutations-sites (RMS) / resistance-mutations-loci (RML) / point mutations(PM), or even against entire resistance-mutations-pattern(s) (RMP-s) of the following , to come HAART or Mega-HAART regimen, respectively.


The polivalent, multivalent, or multivalent-polivalent therapeutic vaccine (PTV-x, MTV-x, MPTV-x) made of killed/highly inactivated HIV-1, bearing on its genome blueprint the resistance-mutations-loci (RML-x)/resistance-mutations-sites (RMS-x), the point-mutations(PM-x), or the whole resistance-mutations-pattern (RMP-x) that would be generated by the following , to come , HAART-x , is pre- administrated to HAART-x, and forms a couple with it : (MPTV -x, HAART-x) or (MPTV-x, Mega-HAART-x) , respectively.


A series, or repeated cycles of (MPTV -x, HAART-x) couples, each couple encompassing a multivalent-polivalent-therapeutic-vaccine (MPTV -x) targeted against/ or encoding /or containing /the in - advance - known resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x) , point-mutations(PM-x), or even the whole resistance-mutations-pattern (RMP-x) of the following, to come HAART-x - regimen (or Mega-HAART-x -regimen , respectively) may lead to the eradication of HIV-1 from the body of any HIV-1 positive person. The expansion of such a successful HIV-1 eradication therapy may save all 40-50 million persons who are HIV-infected worldwide and would solve the HIV/AIDS crisis.

The general HIV-1 eradication scheme in a series and/or multi-cycle scenario is :

(MPTV-1, HAART-1), ----.> (MPTV-2, HAART-2), ----> (MPTV-3,HAART-3),---->........(MPTV-x, HAART-x)........---->
(MPTV-n, HAART-n) ----->
--->(MPTV-1M, Mega-HAART-1),---->( MPTV-2M, Mega-HAART-2), ---->(MPTV-3M, Mega-HAART-3)---->....
....( MPTV-xM, Mega-HAART-x), .... ---->(MPTV-nM, Mega-HAART-n)---> -----> Eradication

clearly indicating that each multivalent, polivalent, or multivalent-polivalent-therapeutic-vaccine (MPTV-x) is pre-administrated to / (precedes) its corresponding HAART-x - regimen (or Mega-HAART-x - regimen respectively), and is targeted against ( or encodes/or contains) the in -advance-known resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x), point-mutations(PM-x), or even the whole resistance-mutations-pattern (RMP-x) that would be generated by the following , to come HAART-x - regimen (or Mega-HAART-x-regimen, respectively) on HIV-1's genome blueprint.

In other words, MPTV-x is preventing the emergence of HAART-x - resistant - virus, acting in fact like a typical VACCINE against the HIV-1 virus that would otherwise emerge after HAART-x therapy. While MPTV-x is preventing the emergence of HAART-x - resistant - virus, HAART-x is reducing viral load, i.e. the numbers of drug-sensitive- virus (DSV).


The synergetic scissoring effect of a (MPTV-x,HAART-x) -couple on HIV-1 may be 1000 or even 10.000 times (3-4 Log) more effective and potent than any current HAART-x - regimen given alone, especially in terms of reducing HIV-1 viral load. Considering that a typical HAART-x regimen is currently able to reduce HIV-1 viral load from 60.000 copies/ml or higher, to 20 copies/ml or lower, a (MPTV-x, HAART-x)-couple might be able to reduce viral loads from 60.000 copies/ml or higher to 2-20 copies/litre, whereas a succession of different (MPTV-x, HAART-x)-couples, may lead to eradication of HIV-1 from the body of HIV-1 positive persons.

In order to better illustrate the potential anti-HIV-1 power of couples formed by a multivalent-polivalent therapeutic vaccine (MPTV-x) and its corresponding HAART-x - regimen , it can be estimated that a single antiretroviral drug like AZT, (or e.g. Crixivan) , would be as effective as 3-4 antiretroviral drugs ( i.e. as effective as HAART ), provided that it is preceded by a multivalent-polivalent-therapeutic-vaccine (MPTV-x) containing killed HIV-1 (or particular parts of HIV-1) bearing on its genome (biochemical structure) the resistance-mutations-pattern(RMP) of AZT.

Figure1/Table1 presents the RMS/RML for different antiretroviral drugs and for 2 drug combinations, i.e. their " point-mutations". The "point-mutations" induced by a particular drug form/build the resistance-mutations-pattern(RMP) of HIV-1 to that drug.


Figure1/Table1

Drug Class
Primary Resistance Mutations
Mutations With Additional Effect


RTIs

AZT (Retrovir®)
M41L, T215Y, T215H
D67N, K70R, K219Q, K219E

3TC (Epivir®)
M184V, M184T, M184I


ddI (Videx®)
L74V
K65R, L74V, V75T, M184V

ddC (HIVID)
K65R
T69D, L74V, V75T, MI84V, Y215C

Abacavir (Ziagen)

K65R, L74V, Y115F, M184V

D4T (Zerit®)
V75T
150T

PFA
E89G, E89K, L921
W88G, W88S, S156A, Q161L, H208Y

NNRTIs

Nevirapine (Viramune®)
K103N, Y181C, Y181I
A98G, L100I, V106A, V108I, Y188C, G190A

Delavirdine (Rescriptor®)
K103N, K103T, Y181C
P23L

Efavirenz (Sustiva)
Y188L
L100I, K101E, K103N, V108I, V179D, Y181C

Protease Inhibitors

Indinavir (Crixivan®)
M46I, M46L, V82A, I84V
L10I, L10R, K20M, K20R, L24I, V32I, I54V, A71V, A71T,
L90M

Nelfinavir (Viracept®)
D30N, M46I, A71V, I84V
M36I, V77I, N88D, L90M

Saquinavir (Fortavase®)
G48V, L90M
L10I, I54V, I84V

Ritonavir (Norvir®)
V82A, V82F, V82S, I84V
K20R, L33F, M46I, I54L, I54V, A71T, A71V, L90M

Resistance to Multiple Drugs

AZT + ddI/ddC
A62V, V75I, F77L, F116Y
Q151M (all 4 mutations required for significant
resistance)

AZT + 3TC
M184V + R211K + L214F
G333D, G333E

A large database containing nearly all published HIV-1 reverse-transcriptase and protease sequences, and that allows
for mutations searching can be found at : http://hivdb.stanford.edu/ (1)

HIV-1 recombination and mutation (2-7), including "resistance-mutation", are important mechanisms by which HIV-1 evades drug or immune pressures. HIV-1- strains that are resistant to an antiretroviral drug present multiple " point-mutations"(PM), which act in synergy to confer the resistant phenotype to that drug, and we may define these "point-mutations" (PM-x) as resistance-mutations-loci (RML-x) or resistance-mutations-sites (RMS-x), whereas their ensemble may be termed resistance-mutations-pattern (RMP-x).

Multidrug resistant HIV-1 strains arise in patients treated with HAART-x or Mega-HAART-x, either through direct mutation or through recombination of variants that are resistant to single drugs.

Paradoxically, and luckily at the same time, point-mutations (PM) that confer drug - resistance offer us targets for vaccine(s) and especially for therapeutic vaccines(TV-s) development. The drug-induced point-mutations (PM), or resistance-mutations-loci (RML-x)/resistance-mutations-sites (RMSx), or even the entire resistance-mutations-patterns (RMP-x-s) may be contained/encoded/encompassed in a multivalent, polivalent or multivalent-polivalent-therapeutic-vaccine (MPTV-x) aimed to prevent the emergence of HAART-x - resistant HIV-1 virus.

In HIV-1 infection, the infected hosts apparently cannot solve the problem of identifying an antigen that is conserved among the variants and quasispecies, and thereby neutralize the infection. Paradoxically and luckily again, both HAART and Mega-HAART regimens are not only reducing HIV-1 viral loads to 50 copies/ml or less, but are also UNIFYING HIV-1's diversity, by "artificially" creating a common factor among the remaining/surviving 50 copies/ml of drug-resistant-virus(DRV), in form of resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x) or point-mutations (PM), which together build the resistance-mutations-pattern (RMP-x).

Each point-mutation (PM) taken separately, and even entire resistance-mutations-patterns (RMP-x-s) are both excellent targets for therapeutic vaccines (TV), and at the same time can be used as a simple, or polyvalent, or multivalent, or multivalent-polyvalent -therapeutic- vaccines (MPTV -x) respectively, namely in form of whole-killed or highly - inactivated HIV-1 virus (Remune-like and/or Remune- modified bearing the HAART-x or Mega-HAART-x mutations ) , bearing on its genome blueprint the resistance-mutations-pattern(s) (RMP-x-s) of the following , next , to come HAART-x or Mega-HAART-x - regimen.

Interestingly and noteworthy, within each (MPTV -x, HAART-x)-couple, and by analogy within each (MPTV-x,Mega-HAART-x)-couple, the multivalent-polyvalent therapeutic vaccine (MPTV -x) acts in fact like a true vaccine, like a CLASSICAL VACCINE against the HAART-x-resistant HIV-1 virus (or Mega-HAART-x- resistant HIV-1 virus), by preventing its emergence.

Each antiretroviral drug and each HAART-x - or Mega-HAART-x - regimen divides the HIV-1 viral population in :
1. drug-sensitive-virus (DSV) , which is killed off by HAART-x or Mega-HAART-x respectively,
and
2. drug-resistant-virus(DRV), whose emergence can be prevented by the multivalent-polyvalent therapeutic vaccine (MPTV -x) which is pre-administrated to its corresponding
HAART-x regimen or Mega-HAART-x regimen, respectively.

If a pre - HAART-x administrated multivalent-polyvalent therapeutic vaccine (MPTV -x) manages to prevent the emergence of drug-resistant-virus(DRV), HIV-1 can be eradicated ,
since the following HAART-x-regimen will eliminate the drug-sensitive- virus(DSV).

Infection and immunity are two sides of the same coin. Therefore it is reasonable and scientifically sound to vaccinate an HIV-1 positive person with killed HIV-1 virus resistant to
a specific HAART-x regimen, before HAART-x treatment ; and with killed wild-type HIV-1 (eventually collected from the patients' blood before HAART-x treatments onset) at the end of all HAART-x or Mega-HAART-x therapies, especially when a long-term structured -treatment - interruption (STI) is planned or intended.

This vaccination with whole, killed, wild-type HIV-1 virus should be done shortly before HAART-x or Mega-HAART-x therapy is stopped ( or interrupted ), since it is well known that some wild-type HIV-1 may still be hidden in certain organs or tissue reservoirs and since it is also well-known that eventually surviving HAART-resistant- HIV-1 virus tends to revert to wild-type HIV-1 virus , after HAART-treatment is stopped.


Two Latin sayings describe the rationale of using (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples in eradication of HIV-1. "Divide et Impera" perfectly describes the role and action of HAART-x and Mega-HAART-x regimens, which divide the
HIV-1 viral population in drug-sensitive-virus(DSV), which is eliminated/cleared by HAART-x and Mega-HAART-x -regimens respectively, and drug-resistant-virus(DRV) , whose emergence is prevented by the multivalent-polyvalent therapeutic vaccine
(MPTV -x) which is pre-administrated to HAART-x or Mega-HAART-x respectively, according to the main principle of prevention, vaccination and homeopathy "Similia Similibus Curentur".

The golden standard for multivalent-polyvalent therapeutic vaccines (MPTV-x)-s to be used in (MPTV -x, HAART-x)-couples or
(MPTV -x,Mega-HAART-x)-couples, should be whole , killed HIV-1 virus or whole, highly inactivated HIV-1 virus
(e.g. Remune-like and Remune-RMP-x- modified), bearing on its genome blueprint the resistance-mutations-pattern(s)
(RMP-x-s), that would be generated by the following , to come HAART-x-regimen.
On the other hand, the ultimate aim of pathogen (HIV-1) -genome sequencing is the development of vaccines. The genome sequence is the"parts list", and each gene or gene product should be tested for its potential usefulness in anti-HIV-1 vaccine and therapeutic vaccine development.

The process of HIV-1 eradication may be divided in 3 steps by monitoring HIV-1 viral load decreases :
STEP 1 would mean a viral load decrease from 60.000copies/ml or highr to 5-50 copies/ml;
STEP 2 would mean a viral load decrease from 5-50 copies/ml to 5-50 copies/litre and
STEP 3 would mean a further viral load decrease from 5-50 copies/litre to zero copies/litre, i.e. eradication of HIV-1. Current HAART and Mega-HAART-x regimens make STEP1 possible for prolonged periods of time. STEP 2 and STEP 3 can only be accomplished by using (MPTV -x, HAART-x)-couples and/or (MPTV -x, Mega-HAART-x) -couples in series and / or cycles.

(MPTV -x) , the multivalent-polyvalent therapeutic vaccines, can be defined and designed in many ways, depending on the drugs that are chosen as partners in the (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples.


When a combination of reverse-transcriptase inhibitors (RTI-s) is chosen as a first-line drug - treatment,(MPTV -x) may contain at least 2 main components :
1. whole killed HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase inhibitor and of their combination (Figure1/Table1) and
2. an HIV-1 reverse-transcriptase enzyme bearing the point-mutations of the following, to come, to be used reverse-transcriptase inhibitors (RTI-s).

When a combination of protease inhibitors is chosen, ,(MPTV-x) may also have 2 main components:
1. whole killed HIV-1 virus bearing the point-mutations (PM) of each protease inhibitor and of their combination(Figure1/Table1) and
2. an HIV-1 protease enzyme bearing the point-mutations (PM) that would be induced by the
following, to come protease inhibitors (PI-s) in the absence of pre-administrated MPTV -x.

When a combination of reverse-transcriptase and protease - inhibitors is chosen as the HAART-x component of the (MPTV-x, HAART-x)-couple, MPTV -x may contain at least 3 main components :
1. whole killed / inactivated HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase and of each protease inhibitor (Figure1/Table1), as well as the point-mutations (PM) with additional effect;
2.an HIV-1 reverse-transcriptase bearing the point-mutations (PM) that would be induced by the reverse-transcriptase inhibitors (RTI-s) to come;
3. an HIV-1 protease enzyme, bearing the point-mutations (PM) that would be induced by the following, to come, to be used protease inhibitors.

In addition to the reverse-transcriptase inhibitors (RTI-s) and protease inhibitors(PI-s), fusion inhibitors like T 20 and T-1249, and integrase inhibitors like S-1360 and L870,810 (8) may be soon added to current HAART-x and Mega-HAART-x regimens. ( The integrase enzyme is essential for HIV to integrate its proviral DNA into the host cell chromosome. S-1360 ,e.g., , is a low molecular weight molecule, for oral use, that inhibits the integrase enzyme in HIV-1.)

An HIV-1 integrase- enzyme, bearing the point-mutations (PM), that would be induced in HIV-1-s genome by integrase inhibitors (II), may be introduced as a fourth component of a multivalent-polyvalent therapeutic vaccine (MPTV -x) against HIV-1, along with :
1. whole killed/inactivated HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase
inhibitor, of each protease inhibitor (Figure1/Table1), and of each integrase inhibitor , as well as the
point-mutations (PM) with additional effect;
2. An HIV-1 reverse-transcriptase bearing the point-mutations (PM) , RMS/RML -s that would be induced by the reverse-transcriptase- inibitors (RTI-s) to come;
3.An HIV-1 protease bearing the point-mutations(PM) ,RMS/RML, and even the whole RMP that would be induced by the following, to come protease inhibitors.


Most importantly in this article , the multivalent-polyvalent therapeutic vaccines (MPTV -x)
may be defined and consist minimally of 3 enzymes :
1. an HIV-1 reverse-transcriptase enzyme,
2. an HIV-1 protease enzyme and
3. an HIV-1 integrase enzyme ,
each of the 3 enzymes bearing the point-mutations (PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x) or even the entire resistance-mutations-patterns (RMP-x-s) of the following , to come HAART-x regimen or Mega-HAART-x regimen, respectively.

Lentivirus HIV-1 encodes three sets of viral proteins : the structural proteins Gag , Pol and Env , the regulatory proteins Tat, Rev and Nef and the maturation proteins Vif, Vpu and Vpr. The structural proteins include the viral envelope proteins (gp120 and gp41) which are encoded by the env gene and the core proteins ( p6, p9, p17, and p24) which are encoded by the gag gene. The pol gene generates the viral associated reverse transcriptase, integrase, RNase H, and protease enzyme activities. The regulatory proteins are encoded by the tat, rev and nef genes respectively. The maturation proteins are encoded by the vif, vpr, and vpu genes. By blocking HIV-1's Pol-encoded Reverse-transcriptase, Protease and Integrase enzymes with couples formed of a Multivalent-Polivalent-Therapeutic-Vaccine (MPTV-x) and its corresponding HAART-x , or Mega-HAART- Regimen, respectively, the entire HIV-1 pol gene could be eliminated.

The rationale to use the 3 viral enzymes : reverse-transcriptase, protease and integrase as components of a multivalent-polyvalent - therapeutic- vaccine (MPTV -x) against HIV-1 is based on the fact that all currently approved antiretroviral drugs are either reverse-transcriptase inhibitors, or protease inhibitors or integrase inhibitors, and only these drugs are able to generate HIV-1 strains bearing on their genomes the point-mutations(PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x), resistance-mutations-patterns (RMP-x-s) listed in Table1/Figure1.

This entirely new approach to treat HIV-1 infections with (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples, can be adapted and used to treat all possible hard - to - treat infectious diseases for which at least one effective drug has been developed, and may lead to the eradication of many (otherwise resistant) microbes, pathogens, viruses and fungi from the body of infected persons.

Especially hard- to- treat infectious diseases, like tuberculosis (TB) and malaria , may be eradicated and drug-resistant pathogens eliminated when (MPTV -x, drugs-x ) -couples are carefully and wisely selected and used rationally.

This (MPTV -x, HAART-x)-couple-approach may also be used in the treatment of cancer. In cancer, the role of the MPTV -x can be taken by killed cancer or particular parts of these cancer cells, bearing on their DNA the mutation-points (MP) of the anti-cancer drugs to be used in chemotherapy.

An entire industry of multivalent therapeutic vaccines (MTV-x), polivalent therapeutic vaccines (PTV-x), and, of course, especially multivalent-polyvalent therapeutic vaccines (MPTV-x)-s against HIV-1 will emerge after the publication of this article. These multivalent-polyvalent therapeutic vaccines (MPTV-x)-s will be used together with their corresponding HAART-x and Mega-HAART-x regimens in (MPTV -x,HAART-x)-couples and (MPTV -x,Mega-HAART-x)-couples, respectively,

Using an "ad conventium" terminology, a polivalent therapeutic vaccine (PTV-x) should have the capacity to prevent the emergence of the primary resistance-mutations-pattern (RMP) for at least one antiretroviral drug and up to a HAART or Mega-HAART -regimen.

A multivalent therapeutic vaccine (MTV-x) should have the capacity to prevent the emergence of at least 2 successive resistance-mutations-patterns (RMP-s) for at least one drug, and up to a HAART or Mega-HAART -regimen, whereas a multivalent-polyvalent therapeutic vaccine (MPTV -x) should be able to prevent the emergence of primary , secondary and even multiple successive HIV-1 resistance-mutations-patterns (RMP-s) for a HAART or Mega-HAART - regimen.

Ideally, a multivalent-polyvalent therapeutic vaccine (MPTV -x) should be able to prevent the emergence of a very high or even unlimited number of successive resistance-mutations-patterns (RMP-s) and/or it should be able eradicate HIV-1 by acting sinergetically with their corresponding HAART-x or Mega-HAART-x regimens, within these (MPTV -x, HAART-x)-couples, or (MPTV-x, Mega-HAART-x)-couples, respectively.

ADVENTRX Pharmaceuticals intends to begin human trials for EradicAide (9) , an HIV therapeutic vaccine, composed of six synthetic peptides, which stimulate a killer T-cell response to clear HIV-infected cells. A unique feature of this treatment is that it is designed to not elicit an antibody response. It is antibody-negative. Such a therapeutic vaccine may be added to (MPTV -x , HAART-x)-couples and (MPTV-x , Mega-HAART-x)-couples , as an adjuvant therapeutic vaccine(ATV).

The Remune vaccine of the The Immune Response Corporation, Inc. (10) may be considered ( and used ) as a possible MPTV -x component in ( MPTV -x , HAART-x )-couples and in (MPTV-x, Mega-HAART-x)-couples . Studies have shown that inactivated, gp120-depleted whole virus immunogen (Remune) boosts immune responses to HIV-1.

Both therapeutic vaccines (TV) mentioned above , (EradicAide and Remune), as well as others that are in advanced development and clinical trials, may eventually be adjusted, modified and adapted to be used in one formulation prior to HAART-x (or Mega-Haart-x) onset, and in a different formulation during HAART-x or Mega-Haart-x treatment. In other words, they may be used both in (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples , and/or as adjuvant therapeutic vaccines(ATV).

Affymetrix (11) , a leading US company in DNA-chip technology has developed GeneChip oligonucleotide probe arrays that are manufactured using a high resolution photolitographic fabrication process adapted from the semiconductor industry, for HIV-1 mutations determinations.
Therion Biologics Corporation (12) recombinant multi-antigen HIV-1 candidate vaccine (TBC-3B) is a live recombinant vaccinia virus vaccine that contains the (env/gag/pol) genes for the major structural and non-structural proteins of HIV , including the matrix, core, nucleocapsid, envelope, reverse transcriptase, integrase, and protease antigens.
Apollon's HIV vaccine program focuses entirely on the DNA approach. The candidate HIV vaccine currently in clinical trials is based on an MN strain of HIV with gp120, gp41 and rev. Additional proteins (such as gag and or pol) may be added to the construct.
Boyer et al (13) have shown that HIV-1 DNA vaccine antigens (env/rev) can stimulate multiple immune responses in vaccine-naive individuals. Such vaccines based on HIV-1 genes may be used as the multivalent-polyvalent -therapeutic- vaccine (MPTV-x) component in (MPTV -x, HAART-x) -couples and (MPTV -x , Mega-HAART-x)-couples, respectively.
The Authors of this article believe that an entire industry of standardized multivalent-polyvalent therapeutic vaccines (SMPTV-x)-s will emerge, to act complementary and sinergetically with HAART-x and/or Mega-HAART-x - regimens in order to eradicate HIV-1.

The Authors of this article are very interested to collaborate with pharmaceutical companies interested to produce (SMPTV -x)-s
for use in (MPTV -x, HAART-x) -couples and (MPTV -x , Mega-HAART-x)-couples aimed and designed to eradicate HIV-1,
all other infectious diseases and even cancer.

References:
1. http://hivdb.stanford.edu/
2. Hahn B.H. , Robertson D.L. , McCutchan F.E. , Sharp P.M. , Recombination and diversity of HIV: implications for vaccine development. Neuvieme Colloque Des Cent Gardes , 1994, 87-94 ;
3. Robertson D.L. , Sharp P.M. , McCutchan F.E. , Hahn B.H. , Recombination in HIV-1, Nature 1995 : 374 :124-126;
4. Robertson D.L. , Hahn B.H. , Sharp P.M. , Recombination in Aids viruses, J.Mol.Evolution , 1995, 40, 249-259;
5. Sharp P.M., Robertson D.L., Hahn B.H. , Cross - species transmission and recombination of ' AIDS ' viruses. , Phil. Trans. R. Soc., London B , 1995, 349 : 41-47;
6. M. L. Kalish et al, Recombinant Viruses and Early Global HIV-1 Epidemic, Emerging Infectious Diseases, Vol.10, No.7, July 2004;
7. I.S. Secasan, D.I. Pop , Fighting HIV with HIV, Medical Hypotheses,1998 Jan;50(1):39-42 Churchill-Livingstone, ISSN 0306-9877;
8. Young, S.D., et al. L870,810: Discovery of a potent HIV integrase inhibitor with potential clinical utility, Presented at The XIV International AIDS, Conference, Barcelona, Spain.
9. http://www.adventrx...._eradicaide.htm
10. http://www.imnr.com : The Immune Response Corporation, Inc. web-site
11. http://www.affymetrix.com/index.affx
12. http://www.therionbio.com, (info@therionbio.com), Therion Biologics Corporation web-site
13. Boyer JD, Cohen AD, Vogt S, Schumann K, Nath B, Ahn L, Lacy K, Bagarazzi ML, Higgins TJ, Baine Y, Ciccarelli RB, Ginsberg RS, MacGregor RR, Weiner DB. Vaccination of seronegative volunteers with a human immunodeficiency virus type 1 env/rev DNA vaccine induces antigen-specific proliferation and lymphocyte production of beta-chemokines. J Infect Dis. 2000 Feb;181(2):476-83.

[granvillestein]

Dear immortality mates: I´m sure it would difficult to me to express a sofisticated correct english. By the way, wouldnt be more plausible to live better than live longer. What about saving our braininformation and retain our genetic storages before we get through the unknown world of non confirmed life after death?

I dreamed to live as long as I could use the media to get intouch with the untouchable... dear mates, let me know your opinions. Yours granvillestein.

[Infernity]

The idea in physical Immortality granvillestein, is that yet it is the only way to have the mental immortality since we yet do not know how to separate.
Moreover, simply some of the things we wanna have in the awareness are things we wanna do physically.

Am I right?

Yours truthfully
~Infernity

[midgehamster]

I wanna go to the stars!

[JonesGuy]

I hear you, Midge.

I'd have to say that space development is one of my favourite topics. I'd say that longevity goes hand-in-hand with seeing space, however. Thus, my interest in both.

[outsider]

Life after death ? There are tons of books that deal with this subject so it's just a mater weither you want to see it or not.

I see myself as being immortal, already. I see every body as immortal.

But in the meantime we can enjoy a better life through supplements, different technics, meditation, sport, moderation etc.

Every one has to chose the tool they want to use to have a good life while it last.

And if you achieve physical immortallity in the meantime good for you. But will you stay inside your house because you are afraid of being hit by a car ? A disaster ?

I think immortallity only makes sense if you are not afraid of dying. And the good news is I feel that as time goes people will be less affraid of dying.

[Infernity]

Outsider,

"What's real is what after stopping believing at- remains real..."

Come back to earth...

And if you achieve physical immortality in the meantime good for you. But will you stay inside your house because you are afraid of being hit by a car ? A disaster ?

No! no, no, no, after all we wanna have immortality for having our awareness including memory- what kinda good memory will we have in such lifestyle?

Did you know that most accidents are homey?

And also- most people die from aging- after we solve that we can work on making our bodies stiffer without dying in the middle so all the research with one's singular outlook goes like nothing. We will improve, don't you worry about that, immortality is a mean more than everything.

~Infernity

[emerald]

I’d like to take a moment to make some societal observations. Much has been said about the negative impacts of indefinite lifespan or negligible senescence. (Kass, Krauthammer, Fukuyama, etc.) So I thought I might add a voice on the positive side. I’ve done many searches but have found little which indicates how a woman’s position in society could change with an indefinite lifespan.

Women were given the right to vote a year after my mother was born. When my mother graduated from high school in 1936 women were expected to be teachers and nurses. These women were expected to step down from their careers should they decide to marry. When WW II was over many women who had been holding down various jobs decided that it was something they didn’t really want to give up. My own mother was an engineering aide at Wright Field during the war. Immediately after the war she pursued a master’s degree in mathematics. In the early 1950’s she was hired as a math instructor at a university. There she and several other women formed a circle of friends. During her time as an instructor she told me that there was an agreement between her and her friends that if a man needed a job, they would willingly step down so that he could provide for his family. She stayed with the university until 1968, when she became pregnant (at the age of 48) with her last child. Shortly after having her baby she ‘retired’ from the university to raise that child-me.

During the mid 1970’s, when the pill became widely used, women’s roles changed dramatically. Childbirth could be delayed until a desired stage in a woman’s career. Now a woman could conceivably stand toe to toe with a male peer. She could –with much more certainty than previous contraceptives- decide not to have children or to postpone having children until a much later stage in life. Thus she could build her career to a desirable point.

With the advent of indefinite lifespan one may also be able to postpone childbearing indefinitely. We can make sperm (ref: “Making Sperm, No Men Necessary” http://www.npr.org/t...toryId=4227604), so I do not think it unreasonable to expect that we would be able to create eggs at some point in the future. It may be possible to create an artificial womb. Can you imagine how this would change a woman’s role in society? Even if artificial wombs can not be created; a women could choose a time of her convenience to have children. There would be absolutely no pressure by a biological clock. Societal expectations to marry and have children would virtually vanish. The illustration of my mother’s life shows how quickly things have been changing. The growing pains from these changes are tremendous and I believe that many people are still attempting to adjust. Some say that indefinite life spans would be detrimental to families. But one must consider what this objection stems from. In our very recent history –and some would say still- a male dominant role in the household was expected. I can not argue that it wouldn’t change families, but I think many changes will be for the best. Parents could ‘retire’ to have children. They could accumulate resources and stay home together to raise their children-if this was their desire. Once the children were old enough they could be retrained and return to the workforce. How could this be a bad thing? Parents could have equal responsibilities in child rearing and the child would have the benefit of potentially many grandparents. Children will become rarer – and more cherished than ever.

Eliminating the female biological clock, via indefinite life spans, means that women really will be equal to men. Many people think that women have made the full journey to equality with men. I think women will travel a great deal further. The number one cause of death of pregnant women is homicide. (source: Journal of the American Medical Association (Vol. 285, No. 11 )) Women are often abused when they need nurturing and support the most. Why would one attempt to preserve this sort of society and hold it above what the future may hold? Society must change. With ageless bodies, people will have a very long time to sort out which mate is best for them and what behaviors are acceptable.

[danpop77]

Winning The Battle Against HIV-1: (MPTV-x , HAART-x) / (MPTV-x , Mega-HAART-x) - Couples Formed of a Multivalent-Polivalent-Therapeutic-Vaccine (MPTV-x) and Its Corresponding HAART-x , or Mega-HAART- Regimen , Respectively.






Iosif Secasan

Department of Urologic Surgery

Spitalul Judetean Resita / The Hospital of Resita

RO-1700, Resita




Dan I. Pop

Data International SRL

Str. Horia, Nr.6, Bl.6, Et.10, Ap.39 Resita-1700, RO-1700, Romania

Phone: 0040-722-940299 E-mail : danpop77@yahoo.com





Ciprian C. Secasan

Department of Microbiology / Department of Urologic Surgery

Spitalul Judetean Resita / The Hospital of Resita

RO-1700, Resita





Abstract : This article presents an entirely new theory and practical solution to eradicate HIV-1, based on HIV-1's ability and need to mutate under HAART-x / Mega-HAART-x drugs pressure, and on the sinergetical scissoring effect on HIV-1 of (MPTV -x , HAART-x) - couples and (MPTV-x , Mega-HAART-x)-couples, which are formed of :

1. a multivalent-polyvalent-therapeutic-vaccine (MPTV -x) , made of whole-killed HIV-1 (or of particular parts of HIV-1) bearing on its genome (biochemical structure) the resistance-mutations-pattern (RMP-x) that would be induced by the following , to come HAART-x or Mega-HAART-x regimen

and of

2. the respective, corresponding HAART-x or Mega-HAART-x regimen, respectively.



Key Words :

HAART (highly-active-anti-retroviral-therapy), HAART-x regimen, Mega-HAART-x regimen, point-mutations (PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x), resistance-mutations-pattern (RMP-x-),

multivalent-polyvalent-therapeutic-vaccine (MPTV -x), (MPTV -x, HAART-x)-couples,

(MPTV-x,Mega-HAART-x)-couples, drug-resistant-virus(DRV) , drug-sensitive-virus (DSV);



Time has come for Science and Medicine to win the battle against HIV and AIDS.

Since a classical vaccine against HIV-1 is hard to design or even define, and since current HAART (highly-active-anti-retroviral-therapy) and even Mega-HAART regimens are unable to clear an HIV-1 infection , a combined strategy has to be adopted, in order to achieve HIV-1 eradication.



This article presents an entirely new theory and practical solution to eradicate the HIV-1 virus from the body of HIV-1 infected persons, by combining HAART (or Mega-HAART) with a multivalent-polivalent -therapeutic-vaccine (MPTV), pre-administrated to HAART, (or Mega-HAART respectively) and targeted against the in-advance-known resistance-mutations-sites (RMS) / resistance-mutations-loci (RML) / point mutations(PM) or even against entire resistance-mutations-pattern(s) (RMP-s) of the following , to come HAART or Mega-HAART regimen, respectively.



The polivalent, multivalent, or multivalent-polivalent therapeutic vaccine (PTV-x, MTV-x, MPTV-x) made of killed/highly inactivated HIV-1, bearing on its genome blueprint the resistance-mutations-loci (RML-x)/resistance-mutations-sites (RMS-x), the point-mutations(PM-x), or the whole resistance-mutations-pattern (RMP-x) that would be generated by the following , to come , HAART-x , is pre- administrated to HAART-x, and forms a couple with it : (MPTV -x, HAART-x) or (MPTV-x, Mega-HAART-x) , respectively.



A series, or repeated cycles of (MPTV -x, HAART-x) couples, each couple encompassing a multivalent-polivalent-therapeutic-vaccine (MPTV -x) targeted against/ or encoding /or containing /the in - advance - known resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x) , point-mutations(PM-x), or the whole resistance-mutations-pattern (RMP-x) of the following, to come HAART-x - regimen (or Mega-HAART-x -regimen , respectively) may lead to the eradication of HIV-1 from the body of a HIV-1 positive person.

The expansion of such a successful HIV-1 eradication therapy may save all 40-50 million persons who are HIV-infected worldwide and would solve the HIV/AIDS crisis.

The general HIV-1 eradication scheme in a series and/or multi-cycle scenario is :

(MPTV-1, HAART-1), ----.> (MPTV-2, HAART-2), ----> (MPTV-3,HAART-3),---->........(MPTV-x, HAART-x)........---->(MPTV-n, HAART-n) ----->

--->(MPTV-1M, Mega-HAART-1),---->( MPTV-2M, Mega-HAART-2), ---->(MPTV-3M, Mega-HAART-3)---->....( MPTV-xM, Mega-HAART-x), ....---->(MPTV-nM, Mega-HAART-n)---> -----> Eradication

clearly indicating that each multivalent, polivalent, or multivalent-polivalent-therapeutic-vaccine (MPTV-x) is pre-administrated to / (precedes) its corresponding HAART-x - regimen

(or Mega-HAART-x - regimen respectively), and is targeted against ( or encodes/or contains) the in -advance-known resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x), point-mutations(PM-x), or even the whole resistance-mutations-pattern (RMP-x) that would be generated by the following , to come HAART-x - regimen (or Mega-HAART-x-regimen, respectively) on HIV-1's genome blueprint.



In other words, MPTV-x is preventing the emergence of HAART-x - resistant - virus, acting in fact like a typical VACCINE against the HIV-1 virus that would otherwise emerge after HAART-x therapy. While MPTV-x is preventing the emergence of HAART-x - resistant - virus, HAART-x is reducing viral load, i.e. the numbers of drug-sensitive- virus (DSV).



The synergetic scissoring effect of a (MPTV-x,HAART-x) -couple on HIV-1 may be 1000 or even 10.000 times (3-4 Log) more effective and potent than any current HAART-x - regimen given alone, especially in terms of reducing HIV-1 viral load. Considering that a typical HAART-x regimen is currently able to reduce HIV-1 viral load from 60.000

copies/ml or higher, to 20 copies/ml or lower, a (MPTV-x, HAART-x)-couple might be able to reduce viral loads from 60.000 copies/ml or higher to 2-20 copies/litre, whereas a succession of different (MPTV-x, HAART-x)-couples, may lead to eradication of HIV-1 from the body of HIV-1 positive persons.



In order to better illustrate the potential anti-HIV-1 power of couples formed by a multivalent-polivalent therapeutic vaccine (MPTV-x) and its corresponding HAART-x - regimen , it can be estimated that a single antiretroviral drug like AZT, (or e.g. Crixivan) , would be as effective as 3-4 antiretroviral drugs ( i.e. as effective as HAART ), provided that it is preceded by a multivalent-polivalent-therapeutic-vaccine (MPTV-x) containing killed HIV-1 (or particular parts of HIV-1) bearing on its genome (biochemical structure) the resistance-mutations-pattern(RMP) of AZT.



Figure1/Table1 presents the RMS/RML for different antiretroviral drugs and for 2 drug combinations, i.e. their " point-mutations". The "point-mutations" induced by a particular drug form/build the resistance-mutations-pattern(RMP) of HIV-1 to that drug.



Figure1/Table1

Drug Class

Primary Resistance Mutations

Mutations With Additional Effect



RTIs



AZT (Retrovir®)

M41L, T215Y, T215H

D67N, K70R, K219Q, K219E



3TC (Epivir®)

M184V, M184T, M184I





ddI (Videx®)

L74V

K65R, L74V, V75T, M184V



ddC (HIVID)

K65R

T69D, L74V, V75T, MI84V, Y215C



Abacavir (Ziagen)



K65R, L74V, Y115F, M184V



D4T (Zerit®)

V75T

150T



PFA

E89G, E89K, L921

W88G, W88S, S156A, Q161L, H208Y



NNRTIs



Nevirapine (Viramune®)

K103N, Y181C, Y181I

A98G, L100I, V106A, V108I, Y188C, G190A



Delavirdine (Rescriptor®)

K103N, K103T, Y181C

P23L



Efavirenz (Sustiva)

Y188L

L100I, K101E, K103N, V108I, V179D, Y181C



Protease Inhibitors



Indinavir (Crixivan®)

M46I, M46L, V82A, I84V

L10I, L10R, K20M, K20R, L24I, V32I, I54V, A71V, A71T,

L90M



Nelfinavir (Viracept®)

D30N, M46I, A71V, I84V

M36I, V77I, N88D, L90M



Saquinavir (Fortavase®)

G48V, L90M

L10I, I54V, I84V



Ritonavir (Norvir®)

V82A, V82F, V82S, I84V

K20R, L33F, M46I, I54L, I54V, A71T, A71V, L90M



Resistance to Multiple Drugs



AZT + ddI/ddC

A62V, V75I, F77L, F116Y

Q151M (all 4 mutations required for significant

resistance)



AZT + 3TC

M184V + R211K + L214F

G333D, G333E

A large database containing nearly all published HIV-1 reverse-transcriptase and protease sequences, and that allows for mutations searching can be found at : http://hivdb.stanford.edu/

HIV-1 recombination and mutation (1-6), including "resistance-mutation", are important mechanisms by which HIV-1 evades drug or immune pressures. HIV-1- strains that are resistant to an antiretroviral drug present multiple " point-mutations"(PM), which act in synergy to confer the resistant phenotype to that drug, and we may define these "point-mutations" (PM-x) as resistance-mutations-loci (RML-x) or resistance-mutations-sites (RMS-x), whereas their ensemble may be termed resistance-mutations-pattern (RMP-x).

Multidrug resistant HIV-1 strains arise in patients treated with HAART-x or Mega-HAART-x, either through direct mutation or through recombination of variants that are resistant to single drugs.

Paradoxically, and luckily at the same time, point-mutations (PM) that confer drug - resistance offer us targets for vaccine(s) and especially for therapeutic vaccines(TV-s) development. The drug-induced point-mutations (PM), or resistance-mutations-loci (RML-x)/resistance-mutations-sites (RMSx), or even the entire resistance-mutations-patterns (RMP-x-s) may be contained/encoded/encompassed in a multivalent, polivalent or multivalent-polivalent-therapeutic-vaccine (MPTV-x) aimed to prevent the emergence of HAART-x - resistant HIV-1 virus.

In HIV-1 infection, the infected hosts apparently cannot solve the problem of identifying an antigen that is conserved among the variants and quasispecies, and thereby neutralize the infection. Paradoxically and luckily again, both HAART and Mega-HAART regimens are not only reducing HIV-1 viral loads to 50 copies/ml or less, but are also UNIFYING HIV-1's diversity, by "artificially" creating a common factor among the remaining/surviving 50 copies/ml of drug-resistant-virus(DRV), in form of resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x) or point-mutations (PM), which together build the resistance-mutations-pattern (RMP-x).

Each point-mutation (PM) taken separately, and even entire resistance-mutations-patterns (RMP-x-s) are both excellent targets for therapeutic vaccines (TV), and at the same time can be used as a simple, or polyvalent, or multivalent, or multivalent-polyvalent -therapeutic- vaccines (MPTV -x) respectively, namely in form of whole-killed or highly - inactivated HIV-1 virus (Remune-like and/or Remune- modified bearing the HAART-x or Mega-HAART-x mutations ) , bearing on its genome blueprint the resistance-mutations-pattern(s) (RMP-x-s) of the following , next , to come HAART-x or Mega-HAART-x - regimen.

Interestingly and noteworthy, within each (MPTV -x, HAART-x)-couple, and by analogy within each (MPTV-x,Mega-HAART-x)-couple, the multivalent-polyvalent therapeutic vaccine (MPTV -x) acts in fact like a true vaccine, like a CLASSICAL VACCINE against the HAART-x-resistant HIV-1 virus (or Mega-HAART-x- resistant HIV-1 virus), by preventing its emergence.

Each antiretroviral drug and each HAART-x - or Mega-HAART-x - regimen divides the HIV-1 viral population in :

1. drug-sensitive-virus (DSV) , which is killed off by HAART-x or Mega-HAART-x respectively,

and

2. drug-resistant-virus(DRV), whose emergence can be prevented by the multivalent-polyvalent therapeutic vaccine (MPTV -x) which is pre-administrated to its corresponding

HAART-x regimen or Mega-HAART-x regimen, respectively.



If a pre - HAART-x administrated multivalent-polyvalent therapeutic vaccine (MPTV -x) manages to prevent the emergence of drug-resistant-virus(DRV), HIV-1 can be eradicated ,

since the following HAART-x-regimen will eliminate the drug-sensitive- virus(DSV).

Infection and immunity are two sides of the same coin. Therefore it is reasonable and scientifically sound to vaccinate an HIV-1 positive person with killed HIV-1 virus resistant to

a specific HAART-x regimen, before HAART-x treatment ; and with killed wild-type HIV-1 (eventually collected from the patients' blood before HAART-x treatments onset) at the end of all HAART-x or Mega-HAART-x therapies, especially when a long-term structured -treatment - interruption (STI) is planned or intended.

This vaccination with whole, killed, wild-type HIV-1 virus should be done shortly before HAART-x or Mega-HAART-x therapy is stopped ( or interrupted ), since it is well known that some wild-type HIV-1 may still be hidden in certain organs or tissue reservoirs and since it is also well-known that eventually surviving HAART-resistant- HIV-1 virus tends to revert to wild-type HIV-1 virus , after HAART-treatment is stopped.



Two Latin sayings describe the rationale of using (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples in eradication of HIV-1. "Divide et Impera" perfectly describes the role and action of HAART-x and Mega-HAART-x regimens, which divide the

HIV-1 viral population in drug-sensitive-virus(DSV), which is eliminated/cleared by HAART-x and Mega-HAART-x -regimens respectively, and drug-resistant-virus(DRV) , whose emergence is prevented by the multivalent-polyvalent therapeutic vaccine

(MPTV -x) which is pre-administrated to HAART-x or Mega-HAART-x respectively, according to the main principle of prevention, vaccination and homeopathy "Similia Similibus Curentur".

The golden standard for multivalent-polyvalent therapeutic vaccines (MPTV-x)-s to be used in (MPTV -x, HAART-x)-couples or (MPTV -x,Mega-HAART-x)-couples, should be whole , killed HIV-1 virus or whole, highly inactivated HIV-1 virus (e.g. Remune-like and Remune-RMP-x- modified), bearing on its genome blueprint the resistance-mutations-pattern(s) (RMP-x-s), that would be generated by the following, to come HAART-x-regimen.

On the other hand, the ultimate aim of pathogen (HIV-1) -genome sequencing is the development of vaccines. The genome sequence is the"parts list", and each gene or gene product should be tested for its potential usefulness in anti-HIV-1 vaccine and therapeutic vaccine development.

The process of HIV-1 eradication may be divided in 3 steps by monitoring HIV-1 viral load decreases :

STEP 1 would mean a viral load decrease from 60.000copies/ml or highr to 5-50 copies/ml;

STEP 2 would mean a viral load decrease from 5-50 copies/ml to 5-50 copies/litre and

STEP 3 would mean a further viral load decrease from 5-50 copies/litre to zero copies/litre, i.e. eradication of HIV-1. Current HAART and Mega-HAART-x regimens make STEP1 possible for prolonged periods of time. STEP 2 and STEP 3 can only be accomplished by using (MPTV -x, HAART-x)-couples and/or (MPTV -x, Mega-HAART-x) -couples in series and / or cycles.

(MPTV -x) , the multivalent-polyvalent therapeutic vaccines, can be defined and designed in many ways, depending on the drugs that are chosen as partners in the (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples.



When a combination of reverse-transcriptase inhibitors (RTI-s) is chosen as a first-line drug - treatment,(MPTV -x) may contain at least 2 main components :

1. whole killed HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase inhibitor and of their combination (Figure1/Table1) and

2. an HIV-1 reverse-transcriptase enzyme bearing the point-mutations of the following, to come, to be used reverse-transcriptase inhibitors (RTI-s).

When a combination of protease inhibitors is chosen, ,(MPTV-x) may also have 2 main components:

1. whole killed HIV-1 virus bearing the point-mutations (PM) of each protease inhibitor and of their combination(Figure1/Table1) and

2. an HIV-1 protease enzyme bearing the point-mutations (PM) that would be induced by the

following, to come protease inhibitors (PI-s) in the absence of pre-administrated MPTV -x.

When a combination of reverse-transcriptase and protease - inhibitors is chosen as the HAART-x component of the (MPTV-x, HAART-x)-couple, MPTV -x may contain at least 3 main components :

1. whole killed / inactivated HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase and of each protease inhibitor (Figure1/Table1), as well as the point-mutations (PM) with additional effect;

2.an HIV-1 reverse-transcriptase bearing the point-mutations (PM) that would be induced by the reverse-transcriptase inhibitors (RTI-s) to come;

3. an HIV-1 protease enzyme, bearing the point-mutations (PM) that would be induced by the following, to come, to be used protease inhibitors.

In addition to the reverse-transcriptase inhibitors (RTI-s) and protease inhibitors(PI-s), fusion inhibitors like T 20 and T-1249, and integrase inhibitors like S-1360 and L870,810 (7) may be soon added to current HAART-x and Mega-HAART-x regimens. ( The integrase enzyme is essential for HIV to integrate its proviral DNA into the host cell chromosome. S-1360 ,e.g., , is a low molecular weight molecule, for oral use, that inhibits the integrase enzyme in

HIV-1.)

An HIV-1 integrase- enzyme, bearing the point-mutations (PM), that would be induced in HIV-1-s genome by integrase inhibitors (II), may be introduced as a fourth component of a multivalent-polyvalent therapeutic vaccine (MPTV -x) against HIV-1, along with :

1. whole killed/inactivated HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase

inhibitor, of each protease inhibitor (Figure1/Table1), and of each integrase inhibitor , as well as the

point-mutations (PM) with additional effect;

2. An HIV-1 reverse-transcriptase bearing the point-mutations (PM) , RMS/RML -s that would be induced by the reverse-transcriptase- inibitors (RTI-s) to come;

3.An HIV-1 protease bearing the point-mutations(PM) ,RMS/RML, and even the whole RMP that would be induced by the following, to come protease inhibitors.



Most importantly in this article , the multivalent-polyvalent therapeutic vaccines (MPTV -x)

may be defined and consist minimally of 3 enzymes :

1. an HIV-1 reverse-transcriptase enzyme,

2. an HIV-1 protease enzyme and

3. an HIV-1 integrase enzyme ,

each of the 3 enzymes bearing the point-mutations (PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x) or even the entire resistance-mutations-patterns (RMP-x-s) of the following , to come HAART-x regimen or Mega-HAART-x regimen, respectively.

The rationale to use the 3 viral enzymes : reverse-transcriptase, protease and integrase as components of a multivalent-polyvalent therapeutic vaccine (MPTV -x) against HIV-1 is based on the fact that all currently approved antiretroviral drugs are either reverse-transcriptase inhibitors, or protease inhibitors or integrase inhibitors, and only these drugs are able to generate HIV-1 strains bearing on their genomes the point-mutations(PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x), resistance-mutations-patterns (RMP-x-s) listed in Table1/Figure1.

This entirely new approach to treat HIV-1 infections with (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples, can be adapted and used to treat all possible

hard - to - treat infectious diseases for which at least one effective drug has been developed, and may lead to the eradication of many (otherwise resistant) microbes, pathogens, viruses and fungi from the body of infected persons.

Especially hard- to- treat infectious diseases, like tuberculosis (TB) and malaria , may be eradicated and drug-resistant pathogens eliminated when (MPTV -x, drugs-x ) -couples are carefully and wisely selected and used rationally.

This (MPTV -x, HAART-x)-couple-approach may also be used in the treatment of cancer.

In cancer, the role of the MPTV -x can be taken by killed cancer cells bearing on their DNA the mutation-points(PM) of the anti-cancer drugs to be used in chemotherapy.

An entire industry of multivalent therapeutic vaccines (MTV-x), polivalent therapeutic vaccines (PTV-x), and, of course, especially multivalent-polyvalent therapeutic vaccines (MPTV-x)-s against HIV-1 will emerge after the publication of this article. These multivalent-polyvalent therapeutic vaccines (MPTV-x)-s will be used together with their corresponding HAART-x and Mega-HAART-x regimens in (MPTV -x,HAART-x)-couples and (MPTV -x,Mega-HAART-x)-couples, respectively,

Using an "ad conventium" terminology, a polivalent therapeutic vaccine (PTV-x) should have the capacity to prevent the emergence of the primary resistance-mutations-pattern (RMP) for at least one antiretroviral drug and up to a HAART or Mega-HAART -regimen.

A multivalent therapeutic vaccine (MTV-x) should have the capacity to prevent the emergence of at least 2 successive resistance-mutations-patterns (RMP-s) for at least one drug, and up to a HAART or Mega-HAART -regimen, whereas a multivalent-polyvalent therapeutic vaccine (MPTV -x) should be able to prevent the emergence of primary , secondary and even multiple successive HIV-1 resistance-mutations-patterns (RMP-s) for a HAART or Mega-HAART - regimen.

Ideally, a multivalent-polyvalent therapeutic vaccine (MPTV -x) should be able to prevent the emergence of a very high or even unlimited number of successive resistance-mutations-patterns (RMP-s) and/or it should be able eradicate HIV-1 by acting sinergetically with their corresponding HAART-x or Mega-HAART-x regimens, within these (MPTV -x, HAART-x)-couples, or (MPTV-x, Mega-HAART-x)-couples, respectively.

ADVENTRX Pharmaceuticals intends now, in 2004, to begin human trials for EradicAide (8) , an HIV therapeutic vaccine, composed of six synthetic peptides, which stimulate a killer

T-cell response to clear HIV-infected cells. A unique feature of this treatment is that it is designed to not elicit an antibody response. It is antibody-negative. Such a therapeutic vaccine may also be added to (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples , as an adjuvant therapeutic vaccine(ATV) to (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples, respectively.

Also, the Remune vaccine of the The Immune Response Corporation, Inc. (9) may be considered ( and used ) as an adjuvant therapeutic vaccine(ATV) to (MPTV -x, HAART-x)-couples and to (MPTV-x,Mega-HAART-x)-couples . Studies have shown that inactivated, gp120-depleted whole virus immunogen (Remune) boosts immune responses to HIV-1.

Both therapeutic vaccines (TV) mentioned above , (EradicAide and Remune), as well as others that are in advanced development and clinical trials, may eventually be adjusted, modified and adapted to be used in one formulation prior to HAART-x (or Mega-Haart-x) onset, and in a different formulation during HAART-x or Mega-Haart-x treatment. In other words, they may be used both in (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples , and/or as adjuvant therapeutic vaccines(ATV).

Affymetrix (10) , a leading US company in DNA-chip technology has developed GeneChip oligonucleotide probe arrays that are manufactured using a high resolution photolitographic fabrication process adapted from the semiconductor industry, for HIV-1 mutations determinations.

The Authors of this article believe that an entire industry of standardized multivalent-polyvalent therapeutic vaccines (SMPTV-x)-s will emerge, to act complementary and sinergetically with HAART-x and/or Mega-HAART-x - regimens in order to eradicate HIV-1.

The Authors of this article are very interested to collaborate with pharmaceutical companies interested to produce (SMPTV -x)-s for use in (MPTV -x, HAART-x) -couples and (MPTV -x , Mega-HAART-x)-couples aimed and designed to eradicate HIV-1, cancer (11) , and other infectious diseases.

References:

1. Hahn B.H. , Robertson D.L. , McCutchan F.E. , Sharp P.M. , Recombination and diversity of HIV: implications for vaccine development. Neuvieme Colloque Des Cent Gardes ,

1994, 87-94 ;

2. Robertson D.L. , Sharp P.M. , McCutchan F.E. , Hahn B.H. , Recombination in HIV-1, Nature 1995 : 374 :124-126;

3. Robertson D.L. , Hahn B.H. , Sharp P.M. , Recombination in Aids viruses, J.Mol.Evolution , 1995, 40, 249-259;

4. Sharp P.M., Robertson D.L., Hahn B.H. , Cross - species transmission and recombination of ' AIDS ' viruses. , Phil. Trans. R. Soc., London B , 1995, 349 : 41-47;

5. M. L. Kalish et al, Recombinant Viruses and Early Global HIV-1 Epidemic, Emerging Infectious Diseases, Vol.10, No.7, July 2004;

6. I.S. Secasan, D.I. Pop , Fighting HIV with HIV, Medical Hypotheses,1998 Jan;50(1):39-42 Churchill-Livingstone, ISSN 0306-9877;

7. Young, S.D., et al. L870,810: Discovery of a potent HIV integrase inhibitor with potential clinical utility, Presented at The XIV International AIDS, Conference, Barcelona, Spain.

8. http://www.adventrx...._eradicaide.htm

9. http://www.imnr.com : The Immune Response Corporation, Inc. web-site

10. http://www.affymetrix.com/index.affx

11. Iosif Secasan, Dan I. Pop, Ciprian C. Secasan: Potentially New And Innovative Treatments For Superficial, Muscle-Invasive, And Metastatic Transitional Cell Carcinoma (TCC) Of The Bladder. The Internet Journal of Oncology. 2005. Volume 2 Number 2.

[arrizza]

Hi Bruce,

I'm new to the group but I've read a lot about what Kurzweil, Moravec etc. are advocating about our transition into becoming machines. In my view this is not the road to immortality but to the eternal enslavement of the human race.


There is a route to immortality that would address all of the issues that pertain to the immortal body living in a finite environment that has been delineated above.

Many of us "think" that immortality is a "physical" state. In fact it's actually an "energy" state. Now here I'm not referring to the soul or spirit or invoking death as is talked about in spiritual circles. What I am talking about is the transmutation of the physical body into its "normal" and "rightful" energy state.

I have been working with a new process for the last 10 years that permanently erases trauma, memory fragments, beliefs negative emotions etc from one's mind/body. The net result is a progressive rejuvenation of the body.

Additionally, what I am finding is that most individuals with whom I work with over a more extended period of time ( upwards of 1 to 2 years) actually start to feel lighter (experience unexplained weight loss) and also begin to appear visually more radiant.

It is my hypothesis that what is happening here is a transmutational process where matter is being converted into energy. Negativity in the form of life trauma, generational trauma and collective human trauma (all stored in the individual's energy field) is what, in my experience, is responsible for the condensation of our natural energy state into finite, mortal physical form. In this form we are then susceptible to and governed by all the laws that govern finite systems.

By transmuting the physical back to its natural energetic state, i.e. who we really are, the difficulties that you and others have outlined above will in my view vanish.

You are welcome to read one of my articles on this at:

http://ezinearticles...rocess&id=43728

Take Care,

Nick Arrizza M.D.

[aeron]

I have a close affinity in concurrence to what Gandalf has written. I too believe in a self that does not cease to be capable of self-awareness that is in perpetual time unlimited growth...now, if I could at the same time extend my physical experience to accommodate my insatiable curiosity, then sign me up and give me a seat on the train. It is all about evolution and learning to me. Just my position statement on the matter. Thank you.
Yours in Trust,
Aeron

[boundlesslife]

(from the initial posting in this thread)...

And physical immortality doesn't just benefit individuals. "Each one of us carries within us a complex universe of knowledge, life experience, and human relationships," says nanotechnology researcher and author Robert A. Freitas. "Almost all of this rich treasury of information is forever lost to mankind when we die."

Freitas arbitrarily equates the amount of knowledge in one's life to that of one book. Considering the fact that each year around 52 million people die and the US Library of Congress holds more than 18 million books, we have a real crisis of knowledge loss. "Each year, we allow a destruction of knowledge equivalent to three Libraries of Congress," says Freitas.

It's really much, much worse than that, depending on how you characterize the information capacity of the brain. With about a hundred trillion synapses, the interconnectivity of which changes dynamically all the time, our "memories" are much more than mere phrases from a book. They are "regenerative" models of our past experiences, that we experience (in some cases) in "virtually" a 'virtual reality' mode.

If we were to hypothesize a computer that could store all of the various scenario recollection content of our brains (try looking at a checkbook register 20 years old, and recalling a particular purchase on one of your vacations, and experience how visions of what went on begin popping into your mind), it would be a stretch of the imagination to set any limits on the data content or processing capacity of that computer by any standard that we presently hold.

Freitas is right about so many things, in such depth, that there is no intent to detract from his example, only (perhaps) to point out that it is *extremely* conservative. Also, it is such a good example, when compounded by the observation of how many of these minds (brains) are lost each year, that it might help us to give our next door neighbors at least some glimmer of the tragedy of death, beyond that which they have learned from the existing culture to attribute to it, and accept as a natural and inevitable consequence of being born.

[Associated observation - for those who haven't seen it yet, "On Intelligence" by Jeff Hawkins (inventor of the Palm Pilot and founder of a neuroscience institute to investigate a new way of looking at how those ~ 100 trillion synapses pull their weight...) is a very eye-opening way of seeing how much more complex our processing of incoming sensory stimulii may be, than we would imagine in terms of more traditional models. I'll add the link to Amazon.Com below, and resist the urge to go further in attempting to arouse interest on the part of any who haven't seen this book.]

On Intelligence

Edited by boundlesslife, 17 November 2005 - 08:49 AM.

[Bruce Klein]

Welcome, boundlesslife.

Thanks for responding. I agree. Relating brains to books is less than adequate... but this may be offset because the analogy is more readily understood. In general, I applaud Freitas for taking the creative leap and for crunching the numbers.

You may be interested in reading Ben Goertzel's take on Hawkings' "On Intelligence"

http://www.goertzel....ntelligence.htm

[boundlesslife]

You may be interested in reading Ben Goertzel's take on Hawkings' "On Intelligence"

http://www.goertzel....ntelligence.htm

That's a great link! Very constructive critique, adding a lot of value by opening up new areas to look at more deeply, for someone (like myself) who hasn't spent the time to look into those areas as deeply as I'd like (yet).

Just before "Engines of Creation" came out, I'd had a look at a prepublication copy and was beginning to feel (as I still do) that brain repair was going to turn out to be more demanding than we could anticipate, and cranked out a short story on the theme that eventually, the whole world would "turn to cryonics", and then be "stumped" as to how to do the reanimation part of it.

So, the story suggested, under pressure from authorities, they finally (the researchers) came up with a scheme to do a kind of primitive "upload" on the brains of some of the best geniuses who had seemed to have great insights as to the repair process, who (of course) were now frozen, and bring just *them* back to solve the problem (with higher-speed thinking). Then, they'd do the actual repair on biological brains and bring back the rest, along with those who they'd generated the initial uploads on.

The picture generated was a little "cyborgy". The uploads were done into "identity modules" that captured just the central cerebral cortex and other core brain functions, and then interfaced with a relatively small number of interconnects to sensory organs and the rest of the body. This little device was inserted into a cavity left by the lack of necessity for much of the bulk of the brain, and a clonal body was "grown around" the device. It was (in the story) easy to back up, and could be upgraded easily, and (best of all) bypassed the need to comingle one's identity with others in a purely "cyberspace" environment.

But, a problem developed. Those they did this with were fully self aware and, far more able to assess the difficulties than any ordinary humans who were working on the problem. They showed that it was not going to be feasible by any stretch of the imagination to actually repair the brains any time soon, if ever, but worst of all, the really *liked" being in that state, because they could think rings around everyone else, had very accelerated memory functions that seemed far more detailed and less prone to "misremembering" than ordinary humans, vivid abilities to picture and create, etc., etc., etc.

Some of their fellow researchers, jealous, "bootstrapped" themselves into the IM state in defiance of regulatory authorities, and then elected to simply freeze their biobrains, once they'd confirmed that they "liked it better". When word of this got out, the whole world went into a frenzy of demand for the process, so that when the central figure in the story woke up and found his friends standing around him, there were very few "biobrain" type people (mainly fundamentalists) left on the planet. The story then hinged on how he "found out" about what had happened, how he reacted, and how he then related to his friends, all of them having been researchers in the field before they were frozen in the first place.

Amongst all of the discussions on uploading and identity, a recurring theme seems to be, "But it wouldn't really be me!" Yet, the burning question would be, "How would you know?" The level of conjectures in terms of atom by atom replacement make it evident that no matter how sophisticated brain repair might turn out to be, to "bring back" a biobrain, *some* very real changes *are* going to be made. So, where does that leave those who are worried that it "won't be them"? I think it leaves them in a pickle of never being reanimated, if they are vocal enough about their demands that it not be done unless it truly "*would* be *them*"!

This has been a bit of a digression from the "why immortality" theme, but in a way, it ties in, because the way aging research is going (too slow), we *all* may wind up facing this problem. When I got involved with cryonics at the age of 34, it seemed like it would take off like crazy. Now, I'm just about to turn 70, and in many ways we're still just getting off the starting line.

Thanks again, Bruce, for the great link to Goertzel's critique. That's going to be a lot of fun to look at, again and again, and to follow the extra links to even more detailed looks at "mind" and "memory".

[Bruce Klein]

Thanks boundlesslife,

I respect and appreciate your long-term commitment to cryonics! I'm only 31, but because of Eric Drexler and Robert Ettinger, I've been thinking about and working toward physical immortality for more than 10 yrs now.

The issue of whether near-term cryopreserved patients will explicitly elect not to uploading because they fear a loss of identity is not that great of a problem in my opinion because most cryonics patients do not stipulate this (before legal death) and because future tech. will be able to adequately maintain identity through high fidelity, atom-by-atom uploading.

[boundlesslife]

The issue of whether near-term cryopreserved patients will explicitly elect not to uploading because they fear a loss of identity is not that great of a problem in my opinion because most cryonics patients do not stipulate this (before legal death) and because future tech. will be able to adequately maintain identity through high fidelity, atom-by-atom uploading.

I'm sure you're right about this, and say what they might in an academic forum, what those who fear uploading might attempt to include in their arrangements on a formal basis would be likely to be far less firm, or, they might be persuaded to at least represent their thoughts on these issues as "strong preferences against" vs. "prohibitions of" repair techniques that went beyond a certain point.

In "LifePact Interviews", we posed questions such as receptivity to accept repair if it would involve the incorporation of a single "artificial neuron", of the 100 billion or so in the brain? Then, progressively we asked about the acceptability of substituting a tiny network of "ten artificial neurons" vs. the originals? And, what about a "hundred artifical neuron" array?

The final option, was, of course, was about the acceptability of "whole brain replacement"? In the process of doing these interviews, with people who were actually making arrangements, we found that there was very little discomfort with leaving the question open, and not attempting to pin down the matter of whether it would "still be them"?

Perhaps this might be owing to the fact that by the time a person gets down to actually making arrangements, they've had to face so many other 'things that could go wrong' and accept the uncertainties of these, that attempting to micromanage the reanimation process seemed irrelevant.

[Bruce Klein]

Right. Also, cryonauts are self-selected for optimists. They have at least enough faith to put money into cryonics... so they are inherently more likely to think that future tech. will allow for successful revival of consciousness.

It's great to have such a long standing immortalist joining us. Again, welcome.