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Mice Put In 'Suspended Animation'


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#1 Matt

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Posted 21 April 2005 - 09:29 PM


Mice put in 'suspended animation'

Mice have been placed in a state of near suspended animation, raising the possibility that hibernation could one day be induced in humans.
If so, it might be possible to put astronauts into hibernation-like states for long-haul space flights - as often depicted in science fiction films.

Posted Image

A US team from Seattle reports its findings in Science magazine.

In this case, suspended animation means the reversible cessation of all visible life processes in an organism.

The researchers from the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle put the mice in a chamber filled with air laced with 80 parts per million (ppm) of hydrogen sulphide (H2S) - the malodorous gas that gives rotten eggs its stink.

Hydrogen sulphide can be deadly in high concentrations. But it is also produced normally in humans and animals, and is believed to help regulate body temperature and metabolic activity.

'Widespread uses'

In addition to its possible use in space travel, the ability to induce a hibernation-like state could have widespread uses in medicine.

Lead investigator Dr Mark Roth said this might ultimately lead to new ways of treating cancer, and preventing injury and death from insufficient blood supply to organs and tissues.

During hibernation, activity in the body's cells slows to a near standstill, dramatically cutting the animal's need for oxygen.

If humans could be freed from their dependence on oxygen, it could buy time for critically ill patients on organ-transplant lists and in operating rooms, said Dr Roth.

"Manipulating this molecular mechanism for clinical benefit potentially could revolutionise treatment for a host of human ills related to ischaemia [deficiency of the blood supply], or damage to living tissue from lack of oxygen," he explained.

But he added that any procedure in a clinical setting would likely be administered via injection rather than by getting patients to inhale a gas.

Astonishing drop


In the latest study, Dr Roth and his colleagues found that the mice stopped moving and appeared to lose consciousness within minutes of breathing the air and H2S mixture.

The animals' breathing rates dropped from the normal 120 breaths per minute to less than 10 breaths per minute.

During exposure their metabolic rates dropped by an astonishing 90%, and their core body temperatures fell from 37C to as low as 11C.

After six hours' exposure to the mixture, the mice were given fresh air. Their metabolic rate and core body temperature returned to normal, and tests showed they had suffered no ill effects.

Co-author Eric Blackstone said the next step would be to carry out studies in larger animals.

Mice do not normally hibernate, but they can reach a similar state called clinical torpor in conditions of food deprivation.

"If you can manipulate the metabolism of animals in this way with implications for humans then I could see very widespread applications," commented John Speakman, professor of zoology at the University of Aberdeen.

"There is military interest in short-duration hibernation for battlefield stabilisation of troops. If you have a soldier who is shot down, you want to be able to hibernate them on site until you can get a team in to rescue them."

Space travel

Scientists at the European Space Agency (Esa) are investigating the possibility of inducing hibernation-like states in astronauts sent on long trips to the outer planets such as Jupiter and Saturn. However, like other applications, this one may be some way off.

"The atmospheric approach to inducing torpor is a nice one because it would diffuse very quickly in the body and saves you having to administer something internally," explained Mark Ayre, of Esa's Advanced Concepts Team at Nordwijk in the Netherlands.

"We have been looking at suspended animation to cut consumables - food and water - on a journey that could take five years or longer. That is important because missions are driven by the mass of the spacecraft.

"The other thing is trying to avoid psychological problems. You can have people awake, in which case you need to keep them entertained. That means more volume and potentially a very large mass.

"Or you avoid all that by putting them to sleep."

Inducing hibernation-like states could also have potential in cancer research by allowing patients to tolerate higher radiation doses without damaging healthy tissue.

Cancer cells are not dependent on oxygen to grow, says Dr Roth, so they are more resistant to radiotherapy.

"Right now in most forms of cancer treatment we're killing off the normal cells long before we're killing off the tumour cells. By inducing metabolic hibernation in healthy tissue, we'd at least level the playing field," he explained.


Edited by Matt, 21 April 2005 - 10:37 PM.


#2 kevin

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Posted 22 April 2005 - 01:43 AM

here's the link to the story..

http://news.bbc.co.u...ure/4469793.stm

#3 JMorgan

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Posted 22 April 2005 - 03:30 AM

I'm curious whether they will attempt a longer period of time than just a few hours. I will REALLY be impressed if they can induce metabolic hibernation for days or months repeatedly with the same mouse and have the mouse live longer as a result.

In other words, can this extend the life of the animal rather than just "pass the time"? It'd be a waste for an astronaut to be put to sleep for a year and then not gain that year back in life expectancy.

Hmm, then again, if we can suspend ourselves indefinitely, how many people will want to be suspended with instructions to be revived in the future so we don't have to sit around and get old waiting for science to catch up with our dreams. ;)

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#4 wraith

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Posted 22 April 2005 - 07:04 PM

I can't find the words to describe how this story makes me feel!!!

I did my MSc on dormancy in marine copepods. I wanted to study intracellular pH and metabolic activation in dormant encysted embryos. Due to intractable methodological issues, I wound up just doing a description of developmental changes in the activated embryos.

But I had my speculations as to the environmental triggers which caused activation. Light was always thought to be the cue, but that made no sense to me, nor did temp changes since I extracted the cysts in darkroom conditions and put them in the fridge. They hatched out anyway, at 5deg C. It had to be one of two things: exposure to O2 or removal of H2S. I'm not sure my speculations (since that's all they were) even made it into my thesis, just my defense and I'm sure no one remembers...

Joy, anguish, all at once. At least someone figured it out. And that it applies to mammals, too! I'd always hoped the intracellular pH stuff would lead to something. This was more than I could ever have hoped for.

#5 JMorgan

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Posted 23 April 2005 - 07:37 AM

Wraith, you are amazing. You actually comprehend all this stuff on a technical basis. I don't understand it at all, but I'm interested anyway. Not to get too off topic, but it's a shame you aren't currently doing something with all that knowledge of yours. (In another thread you mentioned getting a job... is there a lab or university nearby that could use you when you're not taking care of the little one?)

Also, do you think that it would be that much harder to suspend a mouse for a longer period of time, rather than just a few hours? I don't know the biology involved in all this, but for some reason, this article sounded to me like this process is only really usable for short term suspension.

#6 wraith

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Posted 23 April 2005 - 01:37 PM

Longer than six hours, we'll have to wait and see. There's some who say this has been hyped out of all proportion; they're probably right to an extent. That's what the popular press does. But when I presented updates on my copepod cysts I'd always introduce the topic by discussing such far-flung things as organ and tissue preservation. It is fun to think about the possibilities.

As far as lab jobs go, I really don't have the bench skills/experience they're asking for these days. I've applied to a scientific temp agency. Again, wait and see.

#7 JMorgan

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Posted 23 April 2005 - 08:06 PM

Well, wraith, if in the beginning, the job is more to satisfy your time rather than pay bills, volunteer work at a lab would do just the thing. Then, after a few months, you'd have the experience others are looking for. :)

#8 armrha

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Posted 25 April 2005 - 02:10 PM

Even if it's only six hours or less, this has tremendous applications for cryonics patients. With reduced temperature and respiraction, it could give hours to someone who might otherwise decay before a rescue team could get to them.

#9 bgwowk

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Posted 25 April 2005 - 08:03 PM

Even if it's only six hours or less, this has tremendous applications for cryonics patients. With reduced temperature and respiraction, it could give hours to someone who might otherwise decay before a rescue team could get to them.

Cooling is already used in cryonics. The unanswered question of this research, as far as I can see, is whether cooling and H2S is better than just cooling alone.

Note that this research recovered mice after 6 hours at +11 degC. 20 years ago Alcor was recovering *DOGS* after 4 hours at only +4 degC.

http://www.alcor.org...y/html/tbw.html

---BrianW

#10 JMorgan

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Posted 25 April 2005 - 11:33 PM

Alcor was recovering *DOGS* after 4 hours at only +4 degC.

What Alcor did in 1984 was extremely difficult and not without its complications. The important part of the research with these mice is that it's done relatively easily. All the mice do is breathe this stuff, and their bodies shut down automatically. Something this easy to administer gives people the ability to suspend someone who's not near adequate medical facilities.

Also, Alcor artificially cooled the dogs to achieve suspension while the mice cool down naturally as a result of decreased metabolism while in hybernation. The mice also recover rather quickly without much more than breathing fresh air -- an absolutely amazing feat compared to the week of round-the-clock care it took to rehabilitate the dogs.

#11 bgwowk

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Posted 26 April 2005 - 06:27 AM

Something this easy to administer gives people the ability to suspend someone who's not near adequate medical facilities.

There is no escaping the second law of thermodynamics. These mice went down and up from +11 degC so easily because of their high surface area to volume ratio. Without a heart-lung machine, ice bath, or similarly aggressive external cooling, a large animal or human is going to cool then rewarm at approximately one degree *per hour*. And never colder than their ambient environment, needless to say. If H2S is really modulating metabolism, and you don't carefully titrate the dose to correspond to core temperature changes, the result will likely be fatal. No matter how miraculous the stuff, it can never be as easy in large animals as small.

I'm also skeptical that H2S will magically eliminate other problems known to occur in large animal hypothermia, like red blood cell agglutination (why hemodilution is used for deep hypothermia surgery), ventricular fibrilation (heart stopping) below +18 degC, and ion imbalances. I think the mental picture the media has created of this stuff being like just going to sleep and waking up again is wrong for large animals at low temperatures.

I reiterate that it remains be shown whether H2S hypothermic states at any given temperature can be stretched out longer than hypothermic states induced without H2S at the same temperature.

---BrianW

#12 wraith

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Posted 26 April 2005 - 02:24 PM

Yup There will have to be more experiments. There are a lot of questions to be answered. (here's one: Does H2S do more than bind to cytochrome c oxidase?) But it's nice that another avenue of research seems to have opened up, isn't it?

I was trying to find out more on the topic and dug up this (free!) article, a little off-topic but interesting as it considers to the mitochondria & aging problem:

Metabolic integration during the evolutionary origin of mitochondria.
Cell Res. 2003 Aug;13(4):229-38.
Searcy DG.

http://www.ncbi.nlm....t_uids=12974613

#13 wraith

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Posted 26 April 2005 - 02:28 PM

Another free article (which I have yet to read):

From O2 to H2S: a landscape view of gas biology.
Keio J Med. 2002 Mar;51(1):1-10.
Kashiba M, Kajimura M, Goda N, Suematsu M.

The majority of molecular oxygen (O2) consumed in the body is used as a substrate of cytochrome c oxidase to maintain oxidative phosphorylation for ATP synthesis. Rest of the O2 is used for oxidative biosynthesis including synthesis of vasoactive substances such as prostaglandins and secondary gaseous mediators such as nitric oxide (NO) and carbon monoxide (CO). Thus, O2 is not only used for maintenance of energy supply but also for regulating blood supply into tissues. Nitrous oxide (N2O), laughing gas for anesthesia, is generated endogenously through NO reductase in bacteria and fungi, and has recently been shown to modulate N-methyl-D-aspartic acid (NMDA) receptor function. A number of other biologically active gases could participate in regulation of cell and tissue functions. Carbon dioxide (CO2) is generated mainly through the Krebs cycle as a result of glucose oxidation and serves as a potent vasodilator, and hydrogen sulfide (H2S) synthesized through degradation of cysteine has recently been postulated to be a neuromodulator, although their receptor proteins for signaling have not been verified as a discernible molecular entity. Easy penetration allow these gases to access the inner space of receptor proteins and to execute their biological actions. These gases are generated and consumed in anaerobic bacteria through varied reactions distinct from those in mammals. This review summarizes recent information on mechanisms for gas generation and reception in biological systems.
http://www.ncbi.nlm....past/51/1/1.pdf

#14 bgwowk

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Posted 26 April 2005 - 03:34 PM

But it's nice that another avenue of research seems to have opened up, isn't it?

It's a neat trick, no doubt about it.

---BrianW

#15 knite

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Posted 27 April 2005 - 07:51 PM

what body temp are mice normally at?

#16 wraith

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Posted 27 April 2005 - 08:59 PM

http://www.uwm.edu/D...ANUAL/mouse.pdf
96.6° to 99.7° F (35.8° to 37.4° C )




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