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#1 2003-04-27 10:49:48

KaseiII
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From: Uk
Registered: 2003-01-18
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Re: Hibernation - Is human hibernation possible?

I remember reading about a year ago that some scientist, i think in Carolina (though i can't be sure) had stated he had found two genes in human which were used in squirrels during hibernation, and the only thing they needed before human hibernation would be possible was the "trigger", does anyone know if they have found it yet?

Also, does anyone know anyone other (none genetic) ways to induce human hibernation? Or any methods for cryostasis that don't shread your cells? Though i have read an article than says if you replace the nitrogen and CO2 in a cryochamber with hydrogen and helium under a pressure of i think it was about 1500 bars, then you can freeze the person and the Ice will be Ice2, which does not expand like regular ice, hence not shredding your cells, this makes it look like cryostasis could be possible?

So I am asking does anyone have any information on the viability of human hibernation or cryostasis.


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#2 2003-05-05 11:14:06

tim_perdue
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Re: Hibernation - Is human hibernation possible?

I thought they had already successfully frozen and retrieved a dog. Can't be too big of a leap to humans from there can it?

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#3 2003-05-05 13:08:50

RobertDyck
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Re: Hibernation - Is human hibernation possible?

I thought they had already successfully frozen and retrieved a dog. Can't be too big of a leap to humans from there can it?

The last I heard about suspended animation was one attempt to freeze a chipmunk. They did freeze the chipmunk completely and thaw it. It did come back to life, but the cell damage caused it to die just minutes after re-animation. That researcher used a chipmunk because they hibernate. I think this demonstrates that complete cryogenic freezing is not feasible; although theoretically hibernation could permit humans to be "stored" for several months with minimal life support and negligible aging. Other researchers are studying hibernation.

I always suspected that the next major medical breakthrough would be either suspended animation or cloning.

Research into cloning is progressing. The sheep Dolly was a successful cloned mammal. Theoretically the same technology could be used for humans. However, they transferred a nucleus from an adult body cell to an ovum with its nucleus removed, then used an electric shock to initiate cell division. They made no attempt to determine gene masking or other means by which the body cell had been specialized for its particular body function. They also made no attempt to repair the telomeres. The result was most of the fertilized cells died. Dolly was a success, but did suffer from premature aging. Other attempts to clone mammalian farm animals have resulted in various deformities. I believe these deformities are due to retained cell specialization from the donor cell, but that is only my guess. Further research in this area is required.

The cause of the aging problem is known; the process of meiosis that produces gamete cells (ova or sperm) creates an enzyme called telomerase which repairs the telomeres to full length. The telomeres are the ends of the chromosomes. Each cell division cuts off 6 base pairs from each telomere. In humans, the telomeres are long enough for 50 to 100 cell divisions before the telomeres are completely gone. Once the telomeres are gone, the chromosomes unravel and cell division stops. The cell?s metabolism slows, but since it never divides it just grows big; the cell literally becomes fat and lazy. When this happens to a cell it is called senescent, or the cell is said to senesce. When too many of your cells are senescent, your cells cannot replace themselves so tissues cannot repair themselves. This is the primary cause of aging. This means that the telomere is the primary aging clock. The telomere is normally reset to full length during meiosis, which is the creation of an ovum or sperm cell. The cloning process takes a body cell with shortened telomeres and inserts it into a mature ovum; notice this is after telomere repair is over. Cloning a mammal would require the additional treatment of the ovum with telomerase before initiating cell division.

One predicted outcome from human cloning research is organ cloning. This has progressed, and results so far have determined that growing a single organ in-vitro does not involved cloning technology. A plastic replacement for ear cartilage has been developed, which uses scraped skin cells to grow a layer of skin over it. This permitted replacing the outer ear of a patient. The plastic had hormones embedded in it to promote the body to dissolve the plastic, grow cartilage to replace the plastic, and grow blood vessels. As more plastic is dissolved, more hormones are released, causing the body to completely replace the plastic with cartilage and grow blood vessels all the way into the ear. Other researchers have grown a bladder, or a kidney. The kidney is about 40% efficient, but they are working on it. The issues are developing ?scaffolds? to hold the cells in a 3-dimensional shape, and providing a blood supply to all cells before they starve. Notice in-vitro organ growth is an advanced form of tissue culture, not cloning.

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#4 2003-05-05 16:31:39

dickbill
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Re: Hibernation - Is human hibernation possible?

The extend of your scientific knowledge is impressive Robert. I am a biologist and I could not explain better. I just want to add that the technology of stem cells is growing and that is good for the future colons on Mars. Since the radiation/UV level is higher than on Earth, Mars is a little bit cancerogenic from that point of view, but stem cells act like a back up, so I hope that every martian colon could have its frozen stem cells, intact and protected, somewhere in a nitrogen tank.
Already, some hospitals propose to freeze your baby blood cordon (containing stem cells) for, like 70 USdollars a year, so that a stock of intact stem cells is always available for the baby in case of leukemia.
But to come back to the original topic, hibernation is just an induced lethargy with a reduced metabolism at a lower temperature body, but in my opinion, it wouldn't be very useful for just a 3 months trip to mars, because, frankly, if I was lucky enough to do the trip, I wouldn't like to sleep during these 3 months.

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#5 2003-05-06 10:27:22

RobertDyck
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Re: Hibernation - Is human hibernation possible?

The extend of your scientific knowledge is impressive Robert.

Thank you, but my intention was to participate in a real technical discussion; not to show off. I'm pleased someone challenged my post in-vitro organ growth not involving any cloning technology. I was hoping someone would bring up the issue of stem cells; that is the cross-over between organ growth and cloning.

By the way, I hadn't heard the term "cordon" before. I had heard that blood from the umbilical cord contains stem cells. I assume "cordon" refers to that blood.

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#6 2003-05-06 11:51:39

dickbill
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Re: Hibernation - Is human hibernation possible?

I was hoping someone would bring up the issue of stem cells; that is the cross-over between organ growth and cloning.

By the way, I hadn't heard the term "cordon" before. I had heard that blood from the umbilical cord contains stem cells. I assume "cordon" refers to that blood.

yes, blood from the umbilical cord, not cordon.

Cloning to generate an embryo, through the process you explained with its side effets is forbidden for human. The interest to "clone" an adult cell into an enucleated ovocyte is to "reset" the developmental program and differentiation of this cell. If this cell was a skin cell, only able to produce skin cells, then, after the "cloning", it can produce other cell types suitable for tranplantation.  The reason is that this skin cell has become a blastocyst, which now contains multipotent cells in its internal mass which, if implanted in some organs of the  "cloned" adult donor, like the heart or brain, could generate brand new heart or brain cells to rejunevate or cure the organ.
How the reset exactly occurs, it is not known completely, but this is a great subject of interest. Since, if this dedifferentiation process was perfectly known and mastered, it could become possible to reproduce it ouside the context of the ovocyte, then bypass the "embryo cloning" step which is banned. The reason it is banned is obvious since the embryo is potentially an human being if implanted in a foster mother.
But the research should be allowed, otherwise biologists will never know how to dedifferentiate an adult cell and generate stem cells from this adult cell.
I'll talk later about organ growth in culture if I have time.

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#7 2003-05-06 12:47:31

dickbill
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Re: Hibernation - Is human hibernation possible?

Thanks BGD for the help,

Organ culture is a subject I know better. Kidney in particular.
It is a typical developmental biology problem: you have an embryo, it has an immature kidney, how this immature kidney can become fully differentiated and operational ?
One way to experiment is to extract the embryonic kidney from the embryo and put it in culture dish.
If the embryo, not human obviously, is young enough, then its kidney explanted can grow for a time in a petri dish, but in abscence of a natural environment, it doesn't take the shape of a kidney. Ultimately it stops growing and dies, unfortunatly. That shows the limit of a purely in vitro system.

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#8 2003-05-06 13:58:51

dickbill
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Re: Hibernation - Is human hibernation possible?

To finish my speech about cloning, I don't want to show off either, I remember some attempt to clone an adult human cell and make stem cells through a non-human mouse enucleated ovocyte.
After all, we could think that what matters is the genetic content contained in the nucleus. The enucleated ovocyte is mainly cytoplasms, maternal RNA and mitochondria. Adding a human nucleus was like adding the missing genetic information. So that experiment was tempted to show if the transfered human cell could acquire some toti or pluripotency through the passage into the ovocyte. If the embryo was left to divide, it was also expected to become more human cell divivision after cell division, since the only proteins synthetized were under human genetic control, mitochondria excluded, the original murine cytoplasm would become more and more diluted. But ethically it was doubtfull to transfer the resulting embryo into a foster mouse mother, since you would have obtained a mouse pregnant of a potential human being. So, I don't remember very well but I think the nucleus, after a time in the mouse ovocyte, was just retranfered into an enucleated human cell. I have to check that.
The point is: does that cell was now less differentiated, had acquired some pluripotency, after the trip in the mouse egg ?

The problem with those experiment is that there is always some ethical issues and you cannot go very far in cloning technology if you use human cells in any step.
Would any of you be happy if the human/mouse egg had been transfered to a foster female mouse and allowed to divide, maybe until a blastocyste stage ? probably it would die ultimately because the genetic information would not fit with the maternal environment, but some cell divisions could occur with the help of the maternal RNA present in the egg cytoplasm. That would be a strange experiment.

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#9 2003-05-07 10:37:23

dickbill
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Re: Hibernation - Is human hibernation possible?

well, I didn't want to finish the thread about hibernation by talking about cloning.
Hibernation like for a bear or a squirrel might be induced in human, or something close to hibernation, and that could be useful for trip several years long. I checked quickly in the pubmed database and it looks like there are a couple of genes which need to be activated to protect the body from a lower body temperature and lower blood/oxygene flow.
I don't think an hibernation below freezing point is possible in human though. Some animals, fishes and amphibians, can go below zero without freezing, but they are cold blooded and it's not really "hibernation". So I am not sure what kind of hibernation the thread refers, but I am pretty sure we cannot freeze a human being without killing it, or at least killing the cells that matter most for a human being: its neurones.

Low water content cells which do not form ice crystals when they freeze, like sperms, might survive and this is why the russian scientists hoped to "resuscitate" the frozen mamouth that they found in the siberian permafrost. They wanted to transfer the surviving sperms extracted from the  mamouth to enucleated elephant ovocytes, so cloning again, but their attempt failed. Probably the sperms had their DNA content damaged after so long in the ice.
Nobody knows if their is a mamouth in a russian zoo ?

What could have been more reallistic is to extract the surviving  DNA from the frozen sperm and inject it to many feconded elephant ovocytes. That would have created "transgenic" elephants, whith small pieces of mamouth DNA inside their genome. After that , just cross the transgenic elephants between them or inject more of the mamouth DNA into the transgenic and select the offspring for an increase content  in mamouth DNA, generation after generation, something like a mamouth might eventually be obtained. But it's a bit long  and expensive, especially with elephant, but who knows, maybe one day that will be try.

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#10 2003-05-07 11:22:33

dickbill
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Re: Hibernation - Is human hibernation possible?

Correction: Big mistake a wrote, transfering a sperm to an enucleated ovocyte, that wouldn?t work since the resulting genome would be haploid instead of diploid so either the ovocyte was not enucleated or either they use something else than a sperm to transfer to the enucleated ovocyte, like a skin cell nucleus (diploid) or any diploid cell that hasn?t been too much damaged by the thousands of years in the permafrost. It was probably the latter since I remember it was question of an enucleated ovocyte (that was 10 years ago maybe, so forgive the mistake).

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#11 2003-05-07 12:12:32

RobertDyck
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Re: Hibernation - Is human hibernation possible?

I remember hearing that two teams of scientists intended to revive the mammoth species. One intended to use mammoth sperm to fertilize elephant ova; that would have resulted in transgenic elephants. The other intended to clone a mammoth: to transplant the nucleus from a mammoth body cell to an enucleated elephant ovum. Cloning would have resulted in near 100% pure mammoth, but with elephant mitochondria. I didn't hear the result, but the obvious problem would be broken DNA.

One possible solution is to fully sequence the mammoth DNA. The DNA may be fragmented, but the breaks would be in different locations for DNA strands taken from different cells. By simply finding long matching segments, the entire DNA strand can be reconstructed. This only works if you have a large sample of DNA from the same animal: DNA from all cells is supposed to be the same, just broken in different locations. There are certainly a lot of cells in a mammoth. Once the entire chromosomes are mathematically reconstructed, a synthesis machine can build whole DNA strands. This would permit rebuilding whole, intact chromosomes. Replacing just the DNA from a mammoth nucleus, then implanting that into an enucleated elephant ovum could result in a living clone.

Replacing DNA in a nucleus sounds like a tricky procedure. Dickbill, could you tell me if this is necessary, or could bare DNA strands be inserted into an enucleated ovum?

Ps. I got this idea from ?Jurassic Park?, but we do have machines to fully sequence DNA, and to synthesize DNA from a computer data file (mathematical representation).

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#12 2003-05-07 13:01:52

dickbill
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Re: Hibernation - Is human hibernation possible?

I remember hearing that two teams of scientists intended to revive the mammoth species. One intended to use mammoth sperm to fertilize elephant ova; that would have resulted in transgenic elephants. The other intended to clone a mammoth: to transplant the nucleus from a mammoth body cell to an enucleated elephant ovum. Cloning would have resulted in near 100% pure mammoth, but with elephant mitochondria.

The mitochondria are probably so similar that it wouldn't be a problem. You're right, they tried different strategy to 'clone" the mamouth.

I didn't hear the result, but the obvious problem would be broken DNA.

me too, meaning they failed. I hope they are still trying however, because it doesn't sound impossible.

Once the entire chromosomes are mathematically reconstructed, a synthesis machine can build whole DNA strands. This would permit rebuilding whole, intact chromosomes.

unfortunatly we are not here yet. The oligonucleotide synthesis machine effectively add nucleotide after nucleotide, but like every process, it is only efficient at 99%, meaning that after 30/40 bases, some of the synthetized oligonucleotide, have a good chance to have one wrong nucleotide. In a 100 base pair oligo, chances are that a significant % of the oligos have a wrong sequence.
What you could do is to clone small pieces of PCR amplified but exact (some thermophilic resistant polymerases for PCR are almost error proof) fragment of the mamouth genome in DNA plasmid vector. (there are other good stuff to use than the plasmid now, one of the best IMO are BACs, bacterial artificial chromosomes, very efficient). Once the whole mamouth genome has been cloned that way, you can reintroduce it, pieces by pieces in different feconded ovocyte and produce the transgenic animals.

Replacing DNA in a nucleus sounds like a tricky procedure. Dickbill, could you tell me if this is necessary, or could bare DNA strands be inserted into an enucleated ovum?

It depends of what you call replacing. Strictly speaking, replacing an elephant gene by its mamouth homologue requires homologuous recombination, which is indeed very tricky. This is why it is better and simpler to generate transgenic animals. This is a different technique. In transgenesis, you inject with a micropipette the DNA, purified of course, straight into a feconded ovocyte. This is pretty easy with mice, now with elephant, i don't know. But imagine you dispose of hundreds of elephants feconded ovocytes (big job here), you can then reinject the fragments I was talking about. They don't REPLACE the genes, rather, they integrate randomly into the elephant genome. But if the integrated fragment carries a mamouth specific trait, then, this trait can be expressed providing the inserted genes has been engineereed to be expressed.
Technically, that would be insufficient to reconstitute the frozen mamouth, which genome has been splitted and spread among hundred of living elephants, but nothing forbid to cross these elephants togother, some of the offspring might have several mamouth specific characteristics, and really look like a mamouth. Some homologous recombinations, or gene conversion actually, might have occured during the process and it is not impossible that some elephant genes have been really replaced, cleanly, by a mamouth sequence, which would remove the randomness effects of the transgenesis. With mice, that would be very difficult, with elephants...

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#13 2004-10-12 07:38:12

SpaceNut
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Re: Hibernation - Is human hibernation possible?

With further research any thing seems to be possible, understanding the mechanism that allows this to be possible is only part of the answer.

A Sleepy Science: Will Humans Hibernate Their Way Through Space?
http://www.space.com/scienceastronomy/s … 41012.html

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#14 2022-08-01 19:00:24

Mars_B4_Moon
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Registered: 2006-03-23
Posts: 9,776

Re: Hibernation - Is human hibernation possible?

Japanese scientists infused human muscle with a serum from black bears
https://www.tweaktown.com/news/87463/ja … index.html
Japanese researchers have supplemented serum extracted from black bears hibernating into human muscle cells to prevent atrophy.

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