Tuesday, March 23, 2010

The Curious Case of Human Hibernation

Do frost giants protect our glacial sleep?
The survival stories of mountain climbers may be a clue to suspended animation. (Photo by Tim)

Hibernation is a state characterized by inactivity, slower metabolism and lower body temperature. Hibernating animals most often do so to survive food scarcity, especially during the winter. Man is not considered a hibernating animal, but a glance at modern science and strange accounts from the past suggest we may have to revise our views in the future.

James Braid, the father of hypnotherapy and a man with a fascination for the occult, recorded several odd cases of humans surviving hibernation-like conditions in his 1850 book Observations on Trance (link). In his most famous account an Indian fakir was buried alive in the presence of Sir Claude Wade, the English governor at the time. After remaining in the ground for several months, the fakir was reportedly exhumed and restored to consciousness in good health.

No one knows if Braid and Wade were telling the truth, but findings of the same nature have been reported even quite recently. A 1998 paper from Physiology describes two Indian yogis performing similar stunts, although the durations were much shorter (link):

One yogi went into a state of deep bodily rest and lowered metabolism and was able to remain in an airtight box with no ill effects and no sign of tachycardia or hyperpnea for 10 h.

In a different study done in a more naturalistic setting on a different adept, Yogi Satyamurti (70 yr of age) remained confined in a small underground pit, sealed from the top, for 8 days. He was physically restricted by recording wires, during which time electrocardiogram results showed his heart rate to be below the measurable sensitivity of the recording instruments.

A hundred and ten years ago the British Medical Journal ran a short article titled Human Hibernation (link). The article, reprinted in 2000, is a peculiar account of how poor Russian peasants allegedly survive famine by sleeping for half of the year. I'm quoting the full article here:

A Practice closely akin to hibernation is said to be general among Russian peasants in the Pskov Government, where food is scanty to a degree almost equivalent to chronic famine. Not having provisions enough to carry them through the whole year, they adopt the economical expedient of spending one half of it in sleep. This custom has existed among them from time immemorial.

At the first fall of snow the whole family gathers round the stove, lies down, ceases to wrestle with the problems of human existence, and quietly goes to sleep. Once a day every one wakes up to eat a piece of hard bread, of which an amount sufficient to last six months has providently been baked in the previous autumn. When the bread has been washed down with a draught of water, everyone goes to sleep again. The members of the family take it in turn to watch and keep the fire alight.

After six months of this reposeful existence the family wakes up, shakes itself, goes out to see if the grass is growing, and by-and-by sets to work at summer tasks. The country remains comparatively lively till the following winter, when again all signs of life disappear and all is silent, except we presume for the snores of the sleepers.

This winter sleep is called 'lotska'. These simple folk evidently come within '0 fortunatos nimium sua si bona norint!'

In addition to the economic advantages of hibernation, the mere thought of a sleep which knits up the ravelled sleeve of care for half a year on end is calculated to fill our harassed souls with envy. We, doomed to dwell here where men sit and hear each other groan, can scarce imagine what it must be for six whole months out of the twelve to be in the state of Nirvana longed for by Eastern sages, free from the stress of life, from the need to labour, from the multitudinous burdens, anxieties, and vexations of existence.

Don't you just love the poetic style of scientific writing back in those days? The lotska sounds more like an urban legend than an accurate description of lowered metabolism, but in 1906 – six years after the original article appeared – The New York Times ran a story on starving peasants in Russia "lying motionless for days at a time, in order to weaken the pangs of hunger". A few days later, there was a letter to the editor with the following comment on the story (link):

This exigency may be akin to the pseudo-hibernation habitually practiced by Russian peasants in the northern provinces, notably in the Pskov district. If such is the case, the hardships endured by the peasants this Winter may not be as great as the casual reader might be led to believe.

True, the pseudo-hibernation which is general in Pskov has resulted from the fact that famine is well-nigh chronic there; but by pratice from time immemorial the peasants have become accustomed to imitate the habit of the bear and the marmto in Winter, until now the custom is regarded by them as one of the normal conditions of human existence. They have a name for this Winter sleep. It is called "lotska".

In the brief Autumn the housewives prepare a sufficient quantity of hard, black bread to last until Spring. When Winter sets in in earnest the family lie down around the stove and go to sleep. Once in the twenty-four hours everyone wakes up, to nibble at a piece of the black bread, which is washed down with a drink of water. Then all go to sleep again. The members of the family take watch and watch about to keep the fire going.

This pseudo-hibernation lasts until Spring, or upward of six months, when the peasants take up their humble tasks again and are busy until the succeeding Witner, when silence reigns over the frozen land once more.

The writing is somewhat similar to the original 1900 article, but it's not clear whether the writer is the same. Searching for more information on this ancient art of lotska doesn't yield much new, so we're left wondering if the peasants really spent their long winters this way.

The accounts above are of people willingly undergoing depressed metabolism and what might be called a hibernation-like state, but what about people who fall into similar states by accident?

Fast forward about a hundred years, to 1999, when Swedish radiologist Anna Bågenholm got into a skiing accident which left her trapped under a layer of ice (link). For 1 hour 20 minutes, she was in freezing water, suffering the most extreme hypothermia ever recorded in a human. When she was rescued and taken to a hospital, her body temperature was a lethally low 13.7 °C.

After 40 minutes in the icy water, Bågenholm was in cardiac arrest. During cardiac arrest, the normal circulation of blood stops due to failure of the heart to contract effectively. As a result, oxygen is no longer delivered to the body and the brain, which leads to loss of consciousness. Brain injury usually happens after five minutes.

Strangely, despite minor symptoms related to nerve injury, no permanent brain damage was diagnosed in Bågenholm's case. One of the doctors treating her reported that "her body had time to cool down completely before the heart stopped. Her brain was so cold when the heart stopped that the brain cells needed very little oxygen, so the brain could survive for quite a prolonged time."

In 2006, a Japanese man named Mitsutaka Uchikoshi went missing during a mountain climb with friends (link). After leaving his friends to descend the mountain on his own, he tripped and lost consciousness. When he was found 24 days later, his pulse was almost non-existent, his organs had shut down and his body temperature was 22 °C.

Upon hearing his remarkable story, some doctors deemed it physiologically impossible that he had survived for so long without any water. His metabolism had apparently grinded to an almost complete halt. One of the doctors treating him commented: "He fell into a hypothermic state at a very early stage, which is similar to hibernation. Therefore, his brain functions were protected without being damaged and have now recovered 100%. This is what I believe happened".

In late December 2008, Magdeline Makola was abducted and tied up in a car boot (link). After 10 days of drifting in and out of consciousness in below-freezing temperatures, she was found by two traffic police officers. According to doctors, 48 more hours and she would've been dead; in a warmer temperature and she might not have made it through the 10 days. The hypothermia may have saved her life.

In a fascinating TED Talk from 2009, Ken Kamler describes the worst disaster in the history of Mount Everest, and the story of one climber's miraculous survival (link). Due to the fierce wind and extreme conditions, he was not able to return to the base camp from higher up in the mountain and instead just lay there in the snow, too weak to move.

Amidst the chaos, everyone presumed he was dead, until he burst into Kamler's medical tent seemingly out of nowhere, having forced himself to get up and trek back to base camp after 36 hours of being buried in the freezing snow.

Kamler tells the story as an example of the power of the human mind. The climber told him that while laying there in under the snow, he'd thought of his wife and child at home and decided that he couldn't just die there on the mountain. He had to survive for their sake. And so, severely frostbitten and suffering from hypothermia, he somehow managed to not only come back to life but to walk without help to base camp.

The human mind is undoubtedly capable of great things, but reading all these stories, I'm left wondering whether there is something else at play. A recurring theme in many of the cases seems to be that these people's metabolism was slowed down due to freezing temperatures and low oxygen. At mountain altitudes, for example, temperatures and oxygen are lower than at ground level. Even the yogis' tricks were done in small airtight spaces.

For the past years, cell biologist Mark Roth has examined the relationship between oxygen, metabolism and suspended animation. In 2005, he showed that mice exposed to small amounts of hydrogen sulfide put them in a state of hibernation, from which they could be brought back unharmed. The hydrogen sulfide caused the mice's core temperature to drop from 37 °C to 11 °C and their metabolism to slow by 90 percent. Hydrogen sulfide, which is naturally present in the body but toxic at large doses, works by preventing oxygen from binding.

Using freezing temperatures to induce hibernation is generally a bad idea in many species. Warm-blooded animals like humans react to cold by cranking up the internal heating system and burning more oxygen, which spells trouble. According to Roth, the key to lowering metabolism safely is to combine cooling with something that reduces the demand for oxygen (link):
I’m going to be talking [at TED] about unpublished work where we have demonstrated that if you make certain animals cold in an animated state, you kill them. But if you make those same animals cold, but they are now suspended, they all survive.
During the same TED Talk, he mentions experiments showing that if you reduce the oxygen content in the air slightly, roundworms die, and if you reduce it a lot – down to 10 ppm – they stop moving and appear dead but are in fact alive in a state of suspended animation. Unlike their animated and lively friends, these suspended roundworms can be put into cold temperatures without harm.

Exposing an organism to hydrogen sulfide is another way to achieve the same effect as reducing the oxygen content of a container or a room. By binding at the same cell site as oxygen, hydrogen sulfide reduces the need for oxygen, depressing metabolism. Roth theorizes that perhaps hydrogen sulfide production was increased in Bågenholm's own body when she fell under the ice, thus preventing her from dying from the cold.

The first practical application of this technique is surgery, which requires mild hypothermia to prevent harming patients. Even with a small amount of injectable hydrogen sulfide, which Roth's company has developed, the results are apparently better than with a traditional approach. Safety studies are already done, and human trials are underway.

While this is undoubtedly a great medical breakthrough, I can't help but think of other possible applications. What Roth has done is deanimate a mouse by reducing its metabolism and then bring it back to life unharmed. If the human trials are succesful, could this mean hydrogen sulfide might be used even outside surgery? Are we talking about a potential lightweight version of cryonics?

At this point, no one knows. Although similar findings have been confirmed by another lab using mice, two other labs reported that hydrogen sulfide did not induce hibernation in sheep or pigs (link, link), casting doubt on the feasibility of induced hibernation in large mammals.

Also, Roth didn't do lifespan experiments with his mice, so we don't know whether suspending them for longer periods of time might have made them live longer. But given that the connection between lower metabolism and extended lifespan has been shown in several other experiments, I certainly wouldn't be surprised if it did.

Makes you wonder if we could one day be like those poor Russian peasants, sleeping through the hard times and waiting for a brighter future.

For more information on technology and life extension, see these posts:

Biotechnology and the Future of Aging
How to Live Forever: My 5 Steps to Immortality
Aubrey de Grey in Helsinki, Finland
Anti-Aging in the Media: Rolling Stone on Ray Kurzweil

Read More......


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Friday, March 5, 2010

How Do People Feel about Life Extension?

How Do People Feel about Life Extension?
What do you think future societies will look like? (Photo by Tattooed JJ)

If you're a proponent of anti-aging technologies, you most likely know how difficult it can be to argue with people in the pro-aging camp. It sometimes seems that no amount of logical arguments will convince someone who has decided the embrace the idea of dying.

Even though the benefits of increasing human healthspan should be clear to anyone who spends more than a minute thinking about the issue, trying to change public opinion is always a daunting task that takes a long time. If the message you're preaching is true, they will agree with you in the end, but in the meantime, they won't hear a word of it.

I've already written about one global survey on immortality, which indicated that the situation is not quite as hopeless as it could be – the word "immortality" is intimidating to many, after all, and yet there were positive reactions too. But how exactly does the public feel about life extension? If you don't want to live forever, how about living a little bit longer in good health?

This is the question posed by Partridge et al. in their survey, published last year in the Rejuvenation Research journal (link). The team interviewed more than 600 Australians, asking how they felt about the implications of humans being able to live significantly longer. Before the actual questions, the participants were presented with the following vignette:

For this survey, I’d like you to consider the possibility that scientists may develop new biotechnologies to slow down the body’s aging process and vastly increase the length of the human lifespan. This is called life-extension research.

Over the last 100 years or so, better ways to treat and cure diseases have made it possible for people to live longer on average. But, life-extension research aims to
make it possible for people to live much longer lives than we do today, not simply by treating or curing disease, but by slowing down the actual aging process itself. Some scientists estimate that we could live up to 150 years or more by intervening in the rate that we age. By controlling the processes in our body that cause people to age, they claim that we wouldn’t become frail and die at the age we do now, because we wouldn’t deteriorate as quickly. Even though life-extension technologies wouldn’t cure diseases or reverse the ageing process, they may delay the onset of age-related health problems. Ways to slow aging could eventually be offered to people through a range of methods—most likely as life-extension pills.

Imagine what life would be like if scientists developed biotechnologies to slow aging so that people could live past 150 years.

After the vignette, they were asked whether they agree or disagree (on a 7-point scale) with the five questions discussed below. If the participants indicated any level of agreement, they were asked to briefly explain their view and name the most important reasons for their answer.

1. There are ethical or moral issues surrounding life extension research that I find concerning.

More than half (58%) thought that there were some ethical concerns with life extension, the most common being that life extension was "unnatural". Phrases such as "tampering with nature" or "playing God" were common. Second on the list of ethical concerns was the impact of life extension on society and the environment. Overpopulation and lack of sufficient resources were seen as potential problems.

Other ethical concerns included the worry of only rich people having access to life extension technologies and conflicts with religious beliefs. Some participants also felt that funding should be directed to more pressing issues such as treating diseases and poverty, rather than life extension.

2. There would be benefits for me personally from aging slower and living to 150.

Two thirds (64%) thought that a life extension pill would benefit them personally. The most commonly cited benefit was spending more time family members and living to meet future generations of one's family. Almost as many participants saw the ability to experience more things and fulfill life goals as a positive thing.

Being healthier for a longer time was also seen as a benefit, and some felt "living longer" was a benefit that required no further explanation. Only a few (2%) participants named cosmetic improvements as an important benefit, while 7% said they wanted to see what future socities and technologies would look like.

3. There would be downsides for me personally from aging slower and living to 150.

About 80% could name at least one downside to taking a life extension pill. The biggest worry was that the pill would grant extra years of unhealthy life. Living for a long time with a chronic illness was a common fear, as was the uncertainty of physical and mental abilities in someone who is 150.

Second on the list were financial issues with living longer. Many felt that they wouldn't be able to afford to live for many more years. The third problem, identified by 12%, was outliving friends and family: "If I was to take this medication my friends may not take it and you would slowly watch friends die around you.’" Only 5% saw boredom as an issue.

4. Developing life-extension pills would have benefits for society overall.

Half of the participants thought there were some benefits to society from life extension technologies. The most commonly identified benefit was an increase in collective human wisdom and knowledge. The fact that important people such as doctors, scientists, etc. would be around for longer was also seen as a good thing. The third most common benefit was the personal ability to contribute to society more.

5. Developing life-extension pills would have downsides for society overall.

The majority (78%) thought that life extension would have at least some negative consequences for society. Overpopulation was again the most common downside. Participants also felt that health care, housing, food production and welfare would suffer as a consequence, and that there would not be enough resources to support everyone.

Conclusion

The main objection to life extension is still the idea that there is something unnatural and therefore bad about life extension. This thinking seems to be prevalent in religious and non-religious people alike. Other worries include overpopulation and lack of resources in a world where people live significantly longer. Quite a few are also afraid that only the rich will have access to rejuvenation therapies once they become available. Finally, some people worry that these therapies will only prolong unhealthy years, making living longer miserable.

Yet, people also see many positives in life extension. A recurring theme among those surveyed was the ability to spend more time with their family and to live long enough to see their grand-grandchildren grow up. People also felt that a longer life would allow them to experience more things and achieve more of their dreams. Though lack of resources was seen as a problem on the level of societies, many also saw the increase of collective knowledge and the ability to contribute more to society as positive effects of life extension.

And there we have it: the way the average person feels about life extension today. Although seeing the same old pro-aging arguments repeated again and again frustrates me, the fact that so many people were able to see the good things in living longer makes me optimistic. All that is required, then, is to talk to people who have doubts about whether life extension is desirable, to understand where they're coming from, and to get them to open their eyes.

I've already offered some counterarguments to the objections mentioned above in earlier blog posts, but I suppose a more detailed dissection of the arguments is in order. Since most people clearly have the same fears and questions, we might as well learn how to answer them to the best of our abilities. It's about time we break the pro-aging trance, isn't it?

For more information on life extension, see these posts:

Aubrey de Grey in Helsinki, Finland
Why Aging Is a Global Disaster That Needs to Be Solved
Who Wants to Live Forever? Results from a Global Survey
Anti-Aging in the Media: Daily Telegraph on Curing Aging

Read More......


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