Sleep

Guantanamo, Walking the Witch, and How Sleep Deprivation Kills

Research reveals how sleep deprivation can kill.

Posted Jun 22, 2020

 Wikimedia Commons/Public Domain
Matthew Hopkins, Witch Finder General. From a broadside published by Hopkins before 1650.
Source: Wikimedia Commons/Public Domain

We have been going through an unusually challenging year that has seen governmental dysfunction, ecological catastrophe, pandemic illness, economic disaster, global protest, and rapid social change. The year isn’t even half over and the stress on society has been profound. It is little wonder that many people are having difficulty sleeping and are often having frightening dreams when they do. Poor sleep can result in gradually building sleep deprivation that causes serious health and psychological problems. 

A single poor night of sleep can result in irritability, low mood, and less-than-stellar productivity at work. But sleep deprivation can be chronic and build up over time when less than adequate sleep is achieved night after night.

Acute sleep deprivation occurs when sleep is not achieved for a full day or longer. The negative impacts of prolonged sleep deprivation are well known and include psychological, neurological, and physiological effects that affect many bodily systems (Bonnet, 2005). 

Psychologically, sleep deprivation leads to memory difficulties, poor attention and concentration, and low mood. The neurological effects include slowed reaction time that can result in dangerous situations such as motor vehicle accidents. The physiological effects include decreased immunity, weight gain, and increased blood pressure. When we are sleep deprived, the need for sleep becomes an overwhelming obsession. With prolonged deprivation, the need for sleep will begin to exceed the need for food.

The need for sleep will eventually create such a painful and negative emotional state that people will do nearly anything to be able to sleep. For this reason, sleep deprivation has been used as a form of torture for centuries.

For example, during the witch trials in Scotland and England in the 1500s and 1600s, thousands of people, mostly but not exclusively women, were tried for witchcraft and hundreds were executed. Sleep deprivation was used as a technique to obtain confessions. An especially horrible form of this was known as “walking the witch,” in which the victim was forced to keep walking for prolonged periods of time by guards who worked in shifts. The exhaustion, pain, and hallucinatory state caused by several days of this treatment often led to a confession of having committed the crime of witchcraft, frequently with bizarre and fantastic stories of the supposed crimes. 

Apparently, this form of torture was considered relatively mild, at least when compared to other methods that were used. One was “swimming the witch." The purported witches were thrown into a body of water. If they sank, they were considered innocent, and if they floated they were considered guilty. Or the “boots," a torture device in which the victims’ feet were encased and crushed. Matthew Hopkins, who designated himself the “Witchfinder General” used the walking and swimming techniques extensively during his reign of terror in England in the period of 1644 - 1646. Several hundred innocent people died as a result of his efforts.

In modern times, sleep deprivation has continued to be used as a method of extracting information from prisoners. A recent, and shameful, example was the “enhanced interrogation” (torture) program used at Guantanamo Bay, Cuba, during the “global war on terror." At Guantanamo, prisoners were sleep-deprived by hanging them from the ceiling by handcuffs.

Sadly, this program was devised by two psychologists, who were handsomely paid by the CIA for their work. This resulted in significant controversy for the American Psychological Association and ultimately led to the repudiation of psychologists’ involvement in torture. The Obama administration also repudiated these techniques. They are known to be of dubious value for gathering useful information. 

Before the late 1990s, it was believed that people could adapt to prolonged periods of insufficient sleep that was in the range of an average of four to seven hours of sleep per night (Banks, Dorrian, Basner, & Dinges, 2017). This degree of sleep loss was thought to result in increased sleepiness but to have a limited effect on cognitive abilities. More recently (Banks, et al, 2017), however, better controlled and larger studies have shown progressive and significant negative effects of cumulative sleep loss such as poor cognitive function, obesity, diabetes, and hypertension. 

Most often sleep deprivation kills because of accidents. As noted by the CDC, it is estimated that in 2013 drowsy driving resulted in 800 fatalities in the United States but this may be a significant underestimate as the true number may be as much as 6,000 fatal car crashes per year. Commercial drivers and shift workers, which includes nurses and doctors who work the overnight shift, are at especially high risk for motor vehicle accidents.  

Major sleep loss can be tolerated but with significant effects as noted above. In humans, it is not observed to result directly in death. I am unaware of any cases in the medical literature of humans dying directly from the effect of sleep deprivation, although it is possible that the exertion and depletion that could happen with torture like walking the witch could result in death. 

Experimental conditions that have been used in animal studies, however, show that severe sleep deprivation can result in death. In a series of famous studies in the 1980s, it was shown total sleep deprivation of 11-32 days in rats leads to death (Everson, Bergmann, & Rechtschaffen, 1989).

These rats, as compared to yoked controls, appeared to suffer greatly as they appeared debilitated, had low body temperatures, had swelling of their paws, showed motor weakness, had their fur lose color and became oily and clumped together with patches of bare skin between the clumps, developed lesions on their tails and paws, and lost weight despite eating more. Interestingly, no organ pathology was common to all the rats and no obvious cause of death could be determined. 

The researchers found that energy expenditure was increased in the sleep-deprived rats but the cause of death was not clear. When such findings are scaled so as to apply to humans, indications are that humans should better tolerate sleep loss than rats (Bonnet, 2005). This is due to factors such as differences in daily sleep amounts, sleep/wake cycle times, basal energy expenditures, body surface areas, life spans, and survival in the face of other stressors such as starvation.

Estimates based on basal oxygen consumption, for example, would indicate that humans could survive 2 to 7 months of total sleep deprivation before dying (Bonnet, 2005). Combining differences in daily sleep amounts, sleep/wake cycle time, and basal energy expenditures, humans could be expected to survive as much as 2 to 10 years of total sleep deprivation (Bonnet, 2005).

Given the occurrence of microsleeps and the difficulty of causing total sleep deprivation in humans, as well as the finding that animals close to death due to sleep deprivation fully recover if allowed to sleep, it is easy to see why the death of a human due to sleep deprivation per se, is extremely rare, if it occurs at all.

The question remains, however, what caused the deaths of the sleep-deprived experimental animals? We know that sleep affects gastrointestinal functioning (Khanijow, Prakash, Emsellem, Borum, & Doman, 2015) with a strong association between sleep disorders and gastrointestinal diseases such as gastroesophageal reflux disease (GERD), peptic ulcer disease, irritable bowel syndrome, and colorectal cancer. Sleep affects the interaction between the autonomic nervous system and the enteric nervous system that controls digestion. Poor sleep has been shown to alter this interaction and negatively affect digestive health. Poor sleep leads to changes in immune function with the increased production of proinflammatory cytokines. These cytokines have been implicated in gastrointestinal disease. Research has indicated that treating sleep disorders can improve gastrointestinal symptoms. Likewise, treatment of gastrointestinal diseases can improve sleep, as anyone who has ever found themselves awake late into the night because of heartburn associated with GERD and then had their GERD successfully treated is aware.  

New evidence from an animal study gives insight into why sleep deprivation resulted in death in the experimental animals described above. This study, conducted by researchers at Harvard (Vaccaro, Dor, Nambara, Pollina, Lin, Greenberg, & Rogulja, 2020), was conducted using fruit flies, Drosophila melanogaster, a creature that has supplied us with remarkable insights into the genetics of sleep in the past (Allada & Wu, 2017). Mice were also used in the study. This study found that death due to sleep deprivation was always preceded by the accumulation of reactive oxygen species in the gastrointestinal tracts of the fruit flies. 

These chemicals are known to cause significant cell damage and are increased in animals that experience environmental stress. They damage the genetic mechanisms of cells and thus can cause cell death. In the study, control flies lived an average of 40 days while sleep-deprived flies died after 10-20 days of total sleep deprivation. As with the rat study cited above, no obvious internal organ pathology was found in the sleep-deprived flies — except for the buildup of reactive oxygen species in the gut. This buildup in the gut was also demonstrated in the mice that were sleep-deprived. Exactly why sleep deprivation causes this build-up and how it then causes death is unknown and will require further research.

 Wikimedia Commons/Public Domain
"Yin and Yang" by Klem - This vector image was created with Inkscape by Klem, and then manually edited by Mnmazur.
Source: Wikimedia Commons/Public Domain

What was perhaps most exciting about this study was the finding that when the flies were given compounds that neutralize and clear reactive oxygen species from the gut, they were able to remain active and had normal life spans despite being sleep deprived. The supplements given included melatonin and NAD. (For more information on NAD — Nicotinamide Adenine Dinucleotide and its potential for extending the human lifespan, see the article by Rajman, Chwalek, & Sinclair, 2018).

These supplements, however, did not extend the lifespans of non-sleep deprived flies. In addition to the use of supplements, some of the flies were genetically manipulated in order to increase their natural production of antioxidant gut enzymes. For flies that were sleep-deprived, this led to normal or near-normal lifespans despite the deprivation. It did not increase the life spans of the non-sleep deprived flies.

Research such as this is gradually helping scientists better understand the ways in which sleep affects the whole body, and will in time suggest new treatment methods. These are sorely needed in a nation and in a world where so many are suffering from sleep deprivation during these very challenging times. 

References

Allada, R. & Wu, M. (2017). Genetics and genomic basis of sleep in simple model organisms, in Kryger, M, Roth, T, & Dement, W.C. (Eds.), (2017). Principles and Practice of Sleep Medicine sixth edition, Philadelphia: Elsevier, Inc., p 281 – 295.

Banks, S., Dorrian, J., Basner, M., & Dinges, D.F. (2017). Sleep deprivation, in Kryger, M, Roth, T, & Dement, W.C. (Eds.), (2017). Principles and Practice of Sleep Medicine sixth edition, Philadelphia: Elsevier, Inc., p 49 – 55.  

Bonnet, M., (2005). Acute Sleep Deprivation, in Kryger, M, Roth, T, & Dement, W.C. (Eds.), (2005). Principles and Practice of Sleep Medicine fourth edition, Philadelphia: Elsevier, Inc., p. 51 – 66. 

Everson, C. A., Bergmann, B. M., & Rechtschaffen, A. (1989). Sleep deprivation in  the rat: III. Total sleep deprivation. Sleep12(1), 13–21. https://doi.org/10.1093/sleep/12.1.13

Khanijow, V., Prakash, P., Emsellem, H. A., Borum, M. L., & Doman, D. B. (2015). Sleep Dysfunction and Gastrointestinal Diseases. Gastroenterology & hepatology11(12), 817–825.

Rajman, L., Chwalek, K., & Sinclair, D.A. (2018). Cell Metabolism, 27(3), p. 529–547. doi:10.1016/j.cmet.2018.02.011. 

Vaccaro, A., Dor, Y. K., Nambara, K., Pollina, E.A., Lin, C., Greenberg, M. E., & Rogulja, D. (2020). Sleep loss can cause death through accumulation of reative oxygen species in the gut. Cell181(6), p. 1307 – 1328, https://doi.org/10.1016/j.cell.2020.04.049