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The Mole Rat Prophecies

Article #350 • Written by Matt Castle

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The naked mole rat, Heterocephalus glaber, is fleshy, furless, buck-toothed and brazenly ugly. Yet what these small East African rodents lack in terms of good looks, they make up with an impressive array of biological quirks. These misnamed mammals are neither moles nor rats, and in terms of their social behaviour are actually closer to bees, wasps, ants, and termites than to other backboned animals.

They live in underground cooperative colonies of up to 300 individuals with a dominant breeding “queen” and celibate soldier and worker castes. Biologists have identified only one other vertebrate--the closely related Damaraland mole rat--that uses this rigid reproductive and social structure. Until the late 1970s scientists believed that this trait, known as eusociality, was confined to insects.

Naked mole rats deploy several impressive feats of physiology, including an apparent imperviousness to pain, a casual disregard for low-oxygen environments, and resistance to cancer. Indeed, these unsightly creatures both baffle and buttress Darwin's Theory of Evolution in multiple remarkable and apparently self-contradictory ways.

Naked mole rats live almost their entire existence in teeming subterranean tunnels. About the size of a large mouse or a small hamster, they are nearly blind and almost completely hairless. They sport prominent incisors that protrude outside their lips, making effective digging tools. Their tubular, wrinkled body is well formed for moving through narrow passages, and unlike similarly sized animals they can scamper backwards just as easily as they can scurry forwards.

The social structure of a naked mole rat colony mirrors that of a beehive or ant nest, with a single breeding female at its head. Ninety eight percent of the members of a colony will be infertile, with between one and three lucky/exhausted males providing sperm for the sex-obsessed queen. Initially, zoologists believed that the queen curtailed unauthorized reproduction in her subjects by chemical methods, using pheromones in her urine to suppress ovulation in subordinate females. Although odours do play an important friend-or-foe identification role in a mole rat colony, researchers now believe that the queen maintains her breeding monopoly by more direct means: physical abuse. The queen firmly establishes the social hierarchy by head-shoving and clambering over her subordinates. Junior mole rats respond with a physiological stress reaction that effectively suppresses sperm production or ovulation.

Freed of the demands of reproduction, celibate workers can devote their energies to tending to the queen’s young--their siblings, nieces, or nephews--or collecting underground plant tubers to feed the rest of the colony. Meanwhile, higher status rodents form a “soldier caste” that defends the burrow from predatory snakes or foul-smelling foreigner mole rats.

When an old queen dies, the female soldiers engage in blind battle. After much head-butting and clambering, a single victor becomes the new queen and the most powerful males become her royal consorts. Then the young queen grows noticeably larger and longer than her workers, as the vertebrae in her spine spread to accommodate an almost continuous state of pregnancy. To date, researchers have noted neither flickers of lightning nor a stirring Queen soundtrack alongside this surprising physiological process. Relieved of pupcare duties by her celibate minions, she can concentrate on breeding rather than nursing. Almost uniquely among mammals, naked mole rat queens can therefore have litter sizes larger than the number of nipples available for suckling.

The subterranean environment of a mole rat colony helps to explain some of their other notable physiological adaptations. The air inside a crowded mole rat burrow has stuffily high levels of carbon dioxide and suffocatingly low levels of oxygen. The high ambient carbon dioxide concentration increases acid in the rodents’ tissue fluid to levels that would leave most mammals writhing in agony. Researchers discovered that a mutation in a single gene has switched off this response in mole rats, allowing them to adapt to what would otherwise be an extremely uncomfortable environment--and incidentally, giving them a superhero-like resistance to pain. This capability has piqued the interest of medical scientists looking to develop new classes of human painkillers.

Naked mole rats’ tolerance of low oxygen levels also holds promise for improving human health. In most mammals, brain tissue is very sensitive to low oxygen levels, yet a mole rat neuron can survive in conditions of oxygen deprivation, or hypoxia, six times as long as a corresponding mouse neuron--clearly a useful feature in poorly ventilated burrows. Although the mechanisms for this are unclear, it is believed that naked mole rat brain cells retain features of immature but hypoxia-tolerant foetal neurons. Stroke researchers are keen to harness these insights for the treatment of human hypoxic brain injury.

Naked mole rats can live up to 30 years, which is an astonishingly long lifespan for a small rodent— as any hamster or guinea pig enthusiast can attest. Scientists do not fully understand the reasons behind this rodent endurance, although having a low metabolic rate--which may also contribute to their hypoxia tolerance--no doubt helps. In any case, their longevity makes some sense from an evolutionary point of view. Having outsourced reproduction to the queen and her harem, a short lifespan among workers isn't necessary to keep the genetic pool fresh. Task-specialization seems to promote long life, and old age is particularly common among creatures that care for their young communally. These include mole rats, social insects, cave-roosting bats, and humans--which all live much longer than would be expected on the basis of their body mass alone. Furthermore, over-frequent death becomes inconvenient, wasteful, and unsanitary in a crowded burrow. Colony hygiene is paramount when mortality finally asserts itself, and--unusually among non-human mammals--naked mole rats will fastidiously bury their dead.

A naked mole rat tunneling with its teeth
A naked mole rat tunneling with its teeth

Mole rat Methusalehs also benefit from a further biological boon: resistance to cancer. Despite intense scrutiny, scientists have never seen malignant tumours in living Heterocephalus glaber. All attempts to induce tumour growth in unaltered mole rat tissue have failed, despite repeated exposure of mole rat cells to chemical cocktails of potent cancer-causing mutagens. Early studies indicate that mole rats cells may exhibit a form of ‘early contact inhibition’, in which replicating cells recognise their neighbours and cease dividing particularly promptly. This acts as a fail-safe to stop potentially cancerous cells from multiplying beyond a critical density. Researchers are uncertain which evolutionary pressures prompted this improvement, but they are keen to find a way to capitalize on it for humanity.

Despite all these super-rodent powers, not everything goes the mole rats’ way. Thanks in part to their low metabolic rate, they have lost the almost universal mammalian characteristic of individual thermoregulation, and readily catch chills or swoon if temperature in the burrow moves outside of a narrow range. When ambient temperature falls towards 15 degrees centigrade, naked mole rats become sluggish and their body fat starts to solidify. Below 15 degrees, they die. Evolutionarily speaking, this reptilian reversion reflects the “use it or lose it” principle: within the constant 29-30 degree microclimate of their burrow, temperature fluxes are minimal and mole rats have no need for energy-expensive individual temperature regulation.

Leaving their diverse array of unusual physiological features aside, naked mole rats' unorthodox social and reproductive habits pose some difficult questions for scientists. Until the mid 1960s, the existence of social insects, such as bees and ants, posed a strong challenge to the emerging ‘neo-Darwinian synthesis’, which describes the spectacularly neat marriage of Darwin’s theory of evolution with the rapidly expanding field of molecular genetics. The ‘altruistic’ behaviour of sterile worker bees or ants was puzzling. They sacrifice themselves to defend and feed their colony, but with no hope of passing their genes to the next generation. In 1964 a British biologist named William D Hamilton formulated a mathematical rule that appeared to resolve the conundrum.

‘Hamilton’s rule’ is a particularly clear expression of a theory known as kin selection, which states that individuals will sacrifice themselves for others, but only to the extent that those others share their genes. The idea is expressed neatly in the words of another twentieth century biologist, JBS Haldane: “I would lay down my life for two brothers or eight cousins".

Although the majority of evolutionary theorists embrace kin selection, some scientists have offered another idea: that animals can undergo natural selection as a group. ‘Group selection’ theories propose that the same basic evolutionary processes of selection that act on individuals, or their genes, can also act at higher levels of organisation. In other words, the evolutionary ‘unit of selection’ may not always be the gene. Individuals, groups of organisms such as bee or mole rat colonies, or even groups composed of different species could potentially undergo selection collectively. Different versions of group selection theory consider selection at these different levels, and the broader term ‘multilevel selection’ is sometimes used to encompass the full range of possibilities. Such ideas could potentially account for the altruism of social insects and mole rats without needing to invoke kin selection: it is the overall fitness of the group that ultimately determines its survival and transmission of its characteristics to subsequent generations, irrespective of whether individuals within the group share the same genes. In essence, the colony behaves as a single organism from an evolutionary perspective, in much the same way that individual animal cells will readily sacrifice themselves to defend their parent organism.

Altruistic robots
Altruistic robots

Group selection remains greatly contested among biologists: many believe that William Hamilton’s description of kin selection will prove both necessary and sufficient to explain altruism. A Swiss study published in 2011 appears to support their view. A collection of 2 centimeter-high robots were programmed to seek out coloured discs, which represented an analogue for ‘food’. Their randomly configured artificial nervous systems then underwent a simulated form of natural selection, with ‘fitter’ robots more likely to pass their enhanced disc gathering skills to the next generation. Disc-sharing between robots was one of many potential behaviours allowed by the experiment. Over many simulated robot generations, patterns of food sharing emerged akin to the altruism seen in biological systems. Critically, the strength of this altruistic behaviour varied according to the degree of shared ‘inheritance’ between robots, exactly as predicted by Hamilton’s rule.

It is unclear exactly where the decidedly fleshy naked mole rat stands in this controversy. Although individuals within a colony are closely related, they do not share genes as tightly as ‘haplodiploid’ social insects such as bees and wasps, despite showing the same highly developed altruistic behaviour. Whether mole rat eusociality can be explained solely by current interpretations of kin selection or some yet-to-be-fully-developed form of multilevel selection remains to be seen. Nor is it clear that these ideas are mutually exclusive, as they tackle the problem of altruism from very different directions. Either way, the existence of mole rats’ social structure and unique mammalian “reproductive specialization” suggests that eusociality reaches much further into the natural world than first believed— whatever the precise evolutionary mechanisms involved.

Naked mole rats have nevertheless already made an important contribution to validating the basic tenets of evolution--those that no serious biologist would contest--by being successfully 'predicted' to exist. Although mounds of observational evidence and logic support Darwin’s theory of evolution, one nagging question has been its perceived lack of predictive power, often cited as an important feature of any sound scientific theory. An American biologist named Richard Alexander managed to furnish the theory with such predictive proof. Having read William Hamilton's 1964 description of kin selection as an explanation for insect eusociality, he wondered why the phenomenon was not more widespread, particularly among “higher” vertebrate organisms such as mammals and birds. He believed that ‘subsociality’, or the ability to provide parental care, was an essential feature of eusociality.

Given that strong parental impulses are common among mammals, it seemed possible--perhaps even likely--that a set of circumstances could exist in which selective pressures would act to promote eusociality. It just needed a sufficiently harsh and appropriately constrained environment. By applying increasing dollops of deductive logic and well-established Darwinian principles, he was able to identify his hypothesised creatures’ likely location, appearance and behaviour.

Like larger versions of social insects, Alexander speculated that these eusocial mammals would live in nests that were safe, expandable, and close to a localized, easily exploitable supply of food. This suggested an underground colony, as the logs or trees favoured by ants and bees would be too small to accommodate large groups of vertebrates. With the search narrowed down to small burrowing mammals, a rodent species seemed likely.

A naked mole rat queen
A naked mole rat queen

He reasoned that cooperative animals would be better able to exploit concentrated food sources, such as underground plant tubers, rather than dispersed food sources, like the worms favoured by moles and other lone-ranger rodents. Such tubers are common in regions with wet-dry seasons, where plants need a method of storing nutrients and water for use in the dry season. Alexander identified East Africa, with its arid scrub and open woodland, as a promising area with the right type of habitat, climate, and soil to support underground colonies. In such settings, snakes are common predators--and so he expected to see a caste of specialized soldier rodents defending the colony, analogous to soldier ants or termites.

Alexander presented his description in a series of well-attended lectures in the mid-1970s. In 1975, an audience member approached him after the show, and asked if he was aware of the early mole rat research being led by a South African named Jennifer Jarvis. He was not. At that time, Heterocephalus glaber were known as burrowing underground rodents that lived in big groups in East African scrubland, that fed on tubers, and were predated on by snakes. While Jarvis and others had already realised that there was something decidedly unusual about them, the unique reproductive role of the “queen” was not recognized, and nor was the extreme extent of their division of labour. Indeed, Jarvis had become increasingly puzzled and frustrated that only one female would ever breed in her experimental lab colonies. When Alexander contacted her and explained his hypothesis, she finally understood why. Darwin, Hamilton, and Jarvis all played their part in evolving the surprising eusocial answer, and Alexander had successfully predicted a rather unpredictable variety of rodents.

While not unique as an example of evolution’s predictive power, naked mole rats must rank as one of the most curious. Given their record of scientific surprises to date, it seems quite possible that, with further investigation, they may yet offer deeper insights into the exact mechanisms of evolution. In the meantime, it seems equally plausible that Heterocephalus glaber could help a fellow species of African-evolved social mammal discover the secrets of long life, find cures for cancer, protect brains during strokes, resist pain, and--at the very least--develop strategies for efficient nipple use. These remarkable rodents are noteworthy for having challenged and stimulated biologists working in almost every field--from biochemical, physiological, and behavioural science, up to overarching evolutionary theory. These hairless, oddly-reproducing outliers stand as one of evolution’s most unlikely products. The naked mole rats, that is.

Article written by Matt Castle, published on 21 April 2013. Matt is a writer and contributing editor for Damn Interesting, and not quite an anagram of 'Clam Taste'.

Podcast sound design by Alan Bellows. Podcast narration by Simon Whistler. Edited by Alan Bellows.

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Alan Bellows
Posted 24 April 2013 at 06:39 am

As we were working on this article, the frequently excellent Ze Frank released a stimulating video on the naked mole rat, as can be seen here:

Posted 24 April 2013 at 06:44 am

First... I think.

Posted 24 April 2013 at 08:06 am

Nice article. I've known about naked mole rats for years, but I had no idea about their anti-cancer ability or the pain and hypoxia tolerance.

Posted 24 April 2013 at 09:58 am

Hey, I noticed some site updates recently and I was hoping that it foreshadowed some new entries in the Damn Interesting catalog. Yay! :-)

Anyways, fascinating stuff. Everything from the insect-like social behavior, to the physiological pluses and minuses, and especially the fact that they were predicted to exist. Damn interesting, indeed.

The oblique Highlander reference was nice, but the article still needs a picture of Rufus from "Kim Possible". ;-)

Good work, can't wait for more.

Posted 24 April 2013 at 07:12 pm

Interesting article, well done!

Posted 25 April 2013 at 10:49 am

Great article! but there is one sentence I can't make sense of:
"To date, researchers have noted neither flickers of lightning nor a stirring Queen soundtrack alongside this surprising physiological process."
Is there a word missing? or and I just retarded

Posted 25 April 2013 at 10:52 am

IMADR said: "Great article! but there is one sentence I can't make sense of:"To date, researchers have noted neither flickers of lightning nor a stirring Queen soundtrack alongside this surprising physiological process."Is there a word missing? or and I just retarded"

this was the reference to "highlander" that HiEv was talking about. In that movie when 1 immortal killed another it was always followed by lightning striking the winner...

Posted 25 April 2013 at 02:23 pm

matthew1701 said: "IMADR said: "Great article! but there is one sentence I can't make sense of:"To date, researchers have noted neither flickers of lightning nor a stirring Queen soundtrack alongside this surprising physiological process."Is there a word missing? or and I just retarded"

this was the reference to "highlander" that HiEv was talking about. In that movie when 1 immortal killed another it was always followed by lightning striking the winner..."

And I appluad the unexpected reference.

Posted 25 April 2013 at 02:26 pm

matthew1701 said: "IMADR said: "Great article! but there is one sentence I can't make sense of:"To date, researchers have noted neither flickers of lightning nor a stirring Queen soundtrack alongside this surprising physiological process."Is there a word missing? or and I just retarded"

this was the reference to "highlander" that HiEv was talking about. In that movie when 1 immortal killed another it was always followed by lightning striking the winner..."

To expand, the repeated phrase in the movie is "There can only be one", referencing the tournament amoung the Immortals until there was only one left alive (much like the fight between the molerats). Also, Queen did the awesome soundtrack.

Posted 01 May 2013 at 02:33 am

One time I forgot to take my condom off before falling asleep. Those things remind me of what I was looking at the next afternoon (only they have teeth).

Posted 01 May 2013 at 07:47 pm

(from this article) "Relieved of pupcare duties by her celibate minions, she can concentrate on breeding rather than nursing. Almost uniquely among mammals, naked mole rat queens can therefore have litter sizes larger than the number of nipples available for suckling."

(from the Wikipedia article) "The queen nurses them for the first month; after which the other members of the colony feed them feces until they are old enough to eat solid food."

Does the queen then nurse the pups in rotation, I wonder, if she has more pups than nipples? The worker females should not be able to personally help with nursing, since (I presume) they are like other mammals in that their mammary glands are not activated unless they have been pregnant.
Matt, Alan, others -- do you know?
= = = = = = = = = = = =

lydokane, your image reminds me, in a way, of the (fortunately) mythical <a href=""vagina dentata"....

Posted 01 May 2013 at 07:48 pm

Foo--the HTML version of that link didn't work right. See for the discussion of the "vagina dentata".

Matt Castle
Posted 02 May 2013 at 04:13 am

Yes, it seems that Her Majesty suckles very young pups in rotation before they are old enough to be weaned and cared for by other colony members. Because she's pampered and well fed herself, she can spare the time and nutritional resources for an intense breastfeeding schedule. Interestingly, mole rat pups have a correspondingly laid back attitude to feeding— despite the nipple shortage, they appreciate there's plenty to go round and wait patiently in turn without the frenzied jostling that other species' young undergo at suckling time:

Posted 13 May 2013 at 03:57 pm

Thanks. Interesting once again. The story of Alexander was particularly so. Enough so that I was tempted to imagine this article framed by his story, starting with his predictions and then the later discoveries and modern investigations. But, just me wondering.

As no one has plugged it yet, the "hairless, oddly-reproducing outliers... of evolution" that are biologists had me laughing. Thanks again.

Posted 14 May 2013 at 11:34 pm

I saw in the article researchers aren't sure what environmental impact influenced there cancer immunity. this reminded me of an issue that Tasmanian devils are currently having. where they are so closely related they are transmitting cancer to each other. given that the mole rates are incredibly genetically similar, maybe even more so then Tasmanian devils. there cancer immunity may stem from combating similar cancer outbreaks in there population in the past. just some more brain food for ya.

Tasmanian devil cancer link :

Posted 22 May 2013 at 08:27 am

The mole rats and I have something in common - East Africa. Hooray!

Posted 17 June 2013 at 03:39 pm

jakegilmore2006 said: "First... I think."

I hate you, and so should you.

Posted 19 June 2013 at 06:01 pm

Update from today's news (June 19)

NMR tissues were found to be "rich in high molecular weight hyaluronan (HMW-HA)...."

Posted 12 November 2013 at 05:24 pm

I don't think of myslef as a "know" it all, however I did study Biology and Genetics and I'd say that these Mammals (The name does them no Justice and as they're poorly named, I'd prefer to address them as Mammals) are fascinating, impervious to pain, and have slight a slight resistance to cancer. All I want to know is why scientists aren't examining these Mammals and discovering how genetically and Biochemically diiferent they are, you never know, they may hold the cure to cancer as well as unlock secrets about the human mind and body that could have escaped our grasp.

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