(I am republishing a lot of my ‘legacy content’ from our PLOS Neuroanthropology weblog, which has been taken down, along with many of the other founding PLOS Blogs. Some of these, I am putting up because I teach with them. If you have any requests, don’t hesitate to email me at: greg (dot) downey @ mq (dot) edu (dot) au. I suspect many of the links in this piece will be broken, but I will endeavour to try to slowly rebuild this content. Originally published 3 September 2010.)

The photos that accompanied news releases about quadrupedal people living in Turkey, members of a family that allegedly could not walk except on hands and feet, looked staged when I first saw them. Three women and one man scrambling across rocky ground, the women in brightly coloured clothing, the sky radiant blue behind them, their eyes forward and backsides high in the air – like children engaged in some sort of awkward race at a field day or sporting carnival.

For an anthropologist interested in human motor variation and adaptation, the family looked too good to be true. Subsequent reports and a string of papers confirmed that the families did exist, and they suffered from a condition that came to be called ‘Uner Tan Syndrome’ (sometimes ‘Unertan Syndrome’ or UTS). This story is not new, having already broken and exhausted itself on the waves of internet enthusiasm, but I’ve been wanting to write a sober reflection on the lessons I take from UTS for a while now, and my first major post on our new site seems like a good place.

Walking on all fours – we’ve all (or virtually all) done it – but most of us eventually become bipedal, even though the developmental pathways to striding around on two feet vary (see Adolph et al. 2010). The motor pattern is so dominant that bipedalism is considered a defining trait of our species, arising earlier in the paleoarchaeological record than many other distinctive hallmarks of humanity. When I teach my introductory human evolution course, students, like generations of evolutionary theorists, are always surprised by the skeletons of ‘Lucy,’ and now ‘Ardi,’ with ape-like brains and increasingly human-like lower bodies (if they’re not surprised, they pretend to be, probably to humour me).

I’ve previously written about my fascination with human flexibility in movement, including extraordinary forms of mobility (in a piece on the ‘Monkey King,’ an amazing Indian building climber), so Üner Tan, Emeritus Professor from Cukurova University in Turkey and member of the Turkish Academy of Sciences, has been generously sending me pre-print articles and other materials on Uner Tan Syndrome. This piece is made possible by his openness and dogged persistence in spreading the word about this remarkable condition.

Tan first described the syndrome in 2005, based initially on five members of the Ulas family from a small village near Iskenderun, Turkey (seen in those initial photos). He later found families in Adana and small villages near Gaziantep and Canakkale for a total of 14 cases (18 cases in total, but four of which may not have the fully fledged condition from other families) (see Tan 2005; 2006a, b, c; 2010).

From the initial reports, when the number of cases was quite small, Nicholas Humphrey and John R. Skoyles from the London School of Economics and Roger Keynes University of Cambridge, in an LSE discussion paper, opined, ‘even if it is indeed a one-off pathological condition, we think there may be anthropological lessons to be learned from it’ (2005: 11). I couldn’t agree more: although rare (though not ‘one-off’), cases of human quadrupedalism are a fascinating window in on the dynamic developmental processes that so reliably – but not inevitably – produce bipedalism in humans.

Symptoms of Uner Tan Syndrome

In the initial cases of Uner Tan Syndrome, the distinctive and defining symptom of quadrupedalism was accompanied by a number of other cognitive and neurological problems, including especially cerebellar irregularities such as ataxia in the trunk, or the inability to coordinate muscle movement, and intellectual deficits such as delayed or absent speech and ‘conscious experience’ problems.

Humphrey, Skoyles and Keynes (2005: 8 ) reported on a number of the cases and found:

signs of cerebellar dysfunction including: intention tremor, dysdiadochokinesis (inability to execute rapidly alternating movements particularly of the limbs), dysmetria (lack of coordination of movement typified by under- or over-shooting the intended position), and nystagmus (involuntary rhythmic eye movement, with the eyes moving quickly in one direction, and then slowly in the other). However, the cerebellar signs are relatively mild, and they are no more pronounced in the quadrupeds than in the one affected brother who walks bipedally.

MRI and PET scans of a number of the families found inferior cerebellar hypoplasia, an underdevelopment in the cerebellum, particularly the vermis, the narrow area between the two brain hemispheres; mild atrophy in the cerebellar cortex and slightly simplified cerebral gyri, or an overly smooth surface; and a reduced corpus callosum, the white matter structure that connects the hemispheres, in three of the families, but not in the fourth (see Tan et al. 2008). Different subjects seemed to have slightly different anatomical abnormalities, but the consistent neurological abnormalities afflicted primarily the cerebrum and overall gyrification, the parallel ridges, of the cerebellar cortex (see, for example, Ozcelik et al. 2008: 4234).

In spite of their other motor deficits, however, their balance (while quadrupedal, that is) was quite stable and the individuals involved were also capable of fine motor coordination. Some of the women affected, for example, did fine needlework. The fact that they were not more severely affected is important because, as Humphrey, Skoyles and Keynes (2005: 9) point out:

The capacity for walking upright is highly resilient in human beings. In fact humans typically remain bipedal in the face of much greater obstacles to balance and coordination than those experienced by the subjects we have described here. Individuals with bilateral labyrinthine dysfunction, and loss of lower limb proprioceptive sensation are nonetheless typically bipedal. Bipedality can even occur in the complete absence of the cerebellum. There is a recent report of a young man with congenital agenesis of the cerebellum who nevertheless learned to walk and ride a bicycle.

Why can’t they walk?

Because of the pattern of Uner Tan Syndrome within families and its association with consanguineous marriage, or marriage between cousins, most researchers initially suspected that an autosomal recessive gene mutation might be involved.

Sure enough, in 2008 in an article in the Proceedings of the National Academy of Science, Tayfun Ozcelik and colleagues (2008a) reported that the quadrupedal families had a cluster of related genetic abnormalities, mostly to chromosomes 9p24 and 17p, although one affected family did not have abnormalities to either of these chromosomes (for a review, see Tan 2010). In two of the four Turkish families, the abnormality occurred with the VLDLR gene on 9p24, which encodes the very low-density lipoprotein receptor, also implicated in another genetic disorder, Disequilibrium Syndrome (DES-H), where balance and movement problems are also compromised. Although DES-H sufferers have severe walking difficulties, however, no reported cases walk quadrupedally.

Cross-checking against unaffected family members and other members of the community confirmed the likelihood that a mutation to VLDLR might be the culprit, although a cautionary note is that one family member who had the genetic abnormality could walk normally.

VLDLR is involved in the reelin pathway, a glycoprotein regulated mechanisms that moderates neuronal positioning, alignment and migration in the cerebellum; reelin binds to the VLDLR gene and helps get neuroblasts in the right place and configuration for the cerebellum (for a more detailed discussion, see Türkmen et al. 2008). Mice with impaired reelin genes (RELN) or VLDLR abnormalities wind up with abnormal cerebellae, although VLDLR abnormalities can be asymptomatic in mice, only revealed on autopsy (or presumably, if they stuck the little mice in little mice-sized MRIs and got them to sit still) (see Trommsdorff et al. 1999).

However, Ozcelik and colleagues suggested after a thorough gene mapping study that Uner Tan Syndrome was genetically heterogeneous, even in the limited sample of the four Turkish families (2008a: 4234). I’ll come back to that at length in the next post because I think calling every example of habitual and facultative quadrupedalism an example of a single ‘Uner Tan Syndrome’ is misleading, but misleading in a direction that forces us to question whether Uner Tan and others cases of quadrupedalism are actually demonstrating something much broader than a gene causing a disorder, the extreme cases of VLDLR genetic abnormality being only part of the picture.

Tan and colleagues’ (2008) earlier PET and MRI-based study of the original two families likewise showed divergent results: the UTS sufferers in one family had central vestibular deficits, leading to noticeable abnormalities in the brain scans (cerebellar and vermial atrophy and reduced metabolic activity), whereas the second family had peripheral vestibular deficits and ‘quasi-normal’ scans. The team acknowledged that ‘the quadrupedal gait may have different origins, such as developmental delay in the transition from quadrupedality into bipedality during babyhood’ (ibid.: 335). In simple terms, different mechanisms appeared to be producing the extremely unusual results in the families, the development of bipedality stymied by a range of possible obstacles. The diversity was striking because the condition was so rare; if different abnormalities could produce it, why was habitual human quadrupedalism so rare?

Cerebellum problems and gait ataxia

Abnormalities in the cerebellum often lead to gait ataxia or a kind of disordered, ‘drunken’ form of walking. As Morton and Bastian (2007) discuss, damage to the cerebellum likely leads to a number of effects including difficulties in modulating rhythmic movement, even though the movements could be generated by the brainstem and spinal chord. Disruption of this higher order movement orchestration function might explain the instability of walking with cerobellar hypoplasia because, although individuals can produce leg movements, they would have a harder time coordinating the relations between those leg movements. Walking successfully isn’t just doing leg movements but getting the rhythmic oscillations of the limbs synchronized so that one off-step does not disrupt the smooth transfer of weight or trigger a cascade of increasingly awkward or unbalanced movements that might eventually cause the walker to topple over.

In short video clips that Prof. Tan has sent me, a young boy with UTS can be seen standing up and trying to move his feet, but he starts to wobble, apparently due to an inability to control the steps, and quickly falls down. Admittedly, the falling looks well rehearsed, a kind of slumping straight down, as if he isn’t trying to stay up, but that’s likely an effect of his previous experience trying to walk bipedally. In contrast, when walking on hands and feet in another clip, he’s not wobbly at all, but moves smoothly and confidently, quickly getting about a small house.

In addition to coordination problems, damage to some portions of the cerebellum can lead to difficulties maintaining balance in a host of postures, including sitting and standing, as well as walking. The Uner Tan Syndrome cases, however, seem to have problems primarily with walking, and could stand, albeit in awkward positions in some cases. Although vertical posture control conceivably might be compromised to some degree with UTS, the impairment is not so great as to inhibit standing, perhaps because the posture does not exceed the capacities of the impaired cerebellum (patients with cerebellum lesions, however, do often have problems standing upright).

Finally, Morton and Bastian (2007, p. 83) suggest that the cerebellum facilitates adapting movements to perturbations, preserving smooth functioning in shifting situations. Although separating this from the first function in the descriptions of the individuals with Uner Tan Syndrome is difficult, especially working from the published papers alone and a few videotapes, this might also help explain the specific quadrupedal movement. Several of the papers on UTS describe that the subjects could stand but quickly reverted to a four-limbed stance when they tried to step forward. We don’t know if, given ideal situations, the UTS patients might be able to walk, only losing balance when they can’t compensate for variations in conditions. Just judging from the little tape I’ve seen, I think the problem is more profound than this, but it’s hard to tell as learned inability – a lifetime of being unable to walk bipedally – might deter any serious attempt in the older children.

Damage to the cerebellum usually produces distinctive patterns of motor problems; stroke-related insult or gunshot wound to the upper part, for example, can produce problems with gait and balance whereas similar injuries to the lower cerebellum might affect movements of the hands and arms. Fine motor control tends to be affected more by lateral damage; whole body by medial injury.

The Uner Tan Syndrome patients, however, seem to control their bodies, except for their torsos, reasonable well with some issues about aiming movements, tremors, and the like. And yet they lose their ability to walk upright, a remarkably resilient capacity, while developing marked, even extraordinary compensatory facility in quadrupedal movements.

That is, if we focus only on their deficits, we miss the fact that they also have this exceptional ability, one that normal, bipedal humans would be hard-pressed to imitate. Try moving about in a ‘bear walk’ for a while (I have, as the next post will explain), and you’ll quickly realize that, if this is the ‘default’ body position when you can’t balance, most of us have lost the ‘default’ through disuse.

Is Uner Tan Syndrome genetic?

Confronted with the evidence that the genetic abnormalities among the Turkish cases were heterogeneous, and that in one case, an abnormality could not be found, and with a sibling who had the mutation but was able to walk normally, some researchers have concluded that the condition is not solely genetic in origin.

In a working paper (2005) and in a response (2008) to Ozcelik and colleagues’ (2008) piece in PNAS, Humphrey, Skoyles and Keynes offer a more complex etiology for quadrupedalism, one that takes into account the social situation in which a person with equilibrium difficulties finds him- or herself. Humphrey’s team suggests that the ataxia alone would not produce the condition: ‘additional factors must have been at work, operating in the childhood environment, that combined with the ataxia to produce the unprecedented outcome’ (Humphrey et al. 2005: 9).

Humphrey and colleagues (2008: 10) suggest that a convergence of elements more likely explains Uner Tan Syndrome, pointing to a study of children’s movements that highlighted how the ‘bear-crawl’ might form a rare but surprisingly stable intermediate stage that could supersede or entirely replace ‘knee-crawling’:

The bear-crawl has several advantages over more typical knee-crawling, and it can temporarily prove to be an especially good way of getting around. Indeed Ales Hrdlicka, who seventy five years ago wrote a definitive (though now largely forgotten) treatise on this kind of crawling, Children Who Run on All Fours, remarked that “The most common effect of the all- fours method of progression appears to be more or less of a delay in walking erect. . . These children are quite satisfied with their easy and rapid on-all-fours, and were they left to their own devices and not influenced by other examples, they might possibly keep on, on hands and feet, for a longer time if not indefinitely.”

In other words, ‘bear-crawling’ works, so when children discover it (approximately 5% of the time in American children), the development of walking can be delayed because the incentives to abandon quadrupedal movement when doing it on the knees — slowness, difficulty, lack of mobility — are not as great in the ‘bear-crawlers.’ They get better at moving without having to get bipedal.

Humphrey, Skoyles and Keynes (ibid.) go on to suggest a scenario where that ‘bear-crawling’ might continue, potentially into adulthood:

suppose now that an infant who was a bear-crawler were also to have a congenital brain condition which made balancing on two legs unusually difficult. Suppose moreover that such an infant were, in Hrdlicka’s words, to be less than usual “influenced by other examples” (or, more to the point, more than usual influenced by similar examples within its own family), and furthermore that the infant were to be more than usual “left to its own devices” by its caretakers. The stage might well be set for a version of the bear-crawl gait to be carried on into later life, becoming modified and improved until it did in fact become an effective substitute for bipedalism.

As collaborating evidence, although hardly proof, the authors offer that, 1) the mother reported all of her nineteen children were ‘bear-crawlers,’ even those that became bipedal; 2) once one child permanently adopted quadrupedal movement, subsequent children would have had a mature model; 3) the father regarded the children as ‘gifts from God’ with which he could demonstrate love; and 4) a local doctor said that the family passively accepted the condition and did not attempt physiotherapy. Both the third and fourth point would be a point of contention with other researchers.

Türkmen and colleagues (2008: 1073) reach a similar, albeit less elaborate, conclusion after considering the comparison between the Uner Tan Syndrome cases with Disequilibrium Syndrome: although the genetic mutation causing cerebellar hypoplasia and subsequent ataxia is necessary, it is not sufficient to explain human quadrupedalism.

Confronted by Humphrey and his colleagues in a published letter, Ozcelik and his research team (2008b) intensify the argument for a genetic origin for Uner Tan Syndrome. From the final paragraph of their letter, the reason for the intensity of their response is clear: the researchers are aware that some popular accounts of the Turkish families suggest that the parents’ religious beliefs, their understanding of their children’s condition as divinely ordained, contributed to the condition (the authors cite this piece by Anjana Ahuja in The Times Online). Acknowledging developmental dynamics might contribute to a ‘blame the victims’ family (or religion)’ diagnosis. In contrast, Ozcelik and colleagues (2008a: 4236) wrote in the earlier article, and confirm in their letter (2008b), that several of the families actively sought medical and remedial help, including one unaffected sibling who became a physician, and one family discouraged quadrupedal walking without success. (Ironically, Tan 2010: 81, contradicts this assertion.)

Is quadrupedal walking an atavism?

Throughout the discussion of Uner Tan Sydrome, many of the researchers suggest that the quadrupedal walking pattern might be an atavism, a resurgence of a trait from a more distant ancestor that had otherwise disappeared, like a human caudal appendage (a tail) or hind limbs on a dolphin or whale (e.g., Tan et al. 2008; on atavisms, see Hall 1984; specifically on tails, see Bar-Moar et al. 1980). For example, Humphrey and colleagues (2005: 11) ask:

Given that all five individuals developed the same adult gait, as if following the same developmental programme, there are grounds for asking: where could the “memory” for such a programme have come from? Does it in fact represent an atavistic trait, that has been exposed – possibly for the first time in recent human history – by the remarkable conjunction of circumstances?

Brian Hall (1984) defines atavisms as ‘reappearance of a lost character (morphology or behaviour) typical of remote ancestors and not seen in the parents or recent ancestors of the organisms displaying the atavistic character.’ Ironically, although they disagree on the cause of the syndrome, many of the writers seem to agree that quadrupedalism is an evolutionary ‘rediscovery’ or atavism, an assertion which I find pretty difficult to demonstrate.

Prof. Tan (2006c; 2008), himself, has argued that UTS may be a rare case of ‘reverse evolution’ or ‘devolution,’ an argument that has been strongly resisted by other researchers (see, for example, Herz et al. 2008). Most would argue that the concept of ‘devolution’ or ‘reverse evolution’ is simply not coherent, assuming that evolution is normally, necessarily ‘progressive,’ an understanding anathema to some of the most basic evolutionary principles about irreversibility and non-teleology (that evolution isn’t directed ‘progress,’ just variation, survival and change in relation to shifting selectie environments).

In fact, the argument that human ancestors might have once walked on the ground like chimpanzees (knuckle-walking) or walked quadrupedally on the ground at all prior to becoming terrestrial bipeds has been losing ground in recent years as evolutionary theorists increasingly argue that terrestrial bipedalism may have emerged directly from arboreal ways of moving. That is, instead of first descending to the ground and walking like our chimpanzee or gorilla cousins, instead, our ancestors may have developed other forms of aboreal bipedalism and quadrupedalism that they transferred to the ground (see Thorpe et al. 2007; Stanford 2006).

The recent reports about the hand and wrist structure of ‘Ardi,’ the remains of an Ardipithecus ramidus, seem to support the arboreal bipedalism hypothesis and to suggest that palmigrade quadrupedalism may have, in fact, been an ancestral form of locomotion. Ardi’s skeleton demonstrated some of the hallmarks of bipedalism with no trace of the reinforced knuckle and wrist structure that tends to accompany knuckle-walking. Among the long-awaited analyses of Ardi that appeared last year in Science, Owen Lovejoy and colleagues (2009) specifically discussed the forelimb and hand, detailing how this species of hominid might have moved about (for a summary). The long and short is that Ardipithecus likely moved quadrupedally in trees (carefully walking atop branches) and bipedally on the ground, although this is subject to dispute.

If Ardipithecus was an arboreal quadruped and a terrestrial biped, the argument that terrestrial quadrupedalism is an atavism starts to look a little less convincing. Either we’d have to assume that the pattern of ground movement is a very, very old atavism, predating the move of primate ancestors into an arboreal niche (and thus probably predating the rise of true primates somewhere around 50-80 mya) or disregard the mechanical differences between moving in trees and moving on the ground, including the importance of grasping branches while moving (which Ardipithecus would have been able to do with both hands and feet).

I’m less convinced of the argument that quadrupedalism is an ‘atavism’ because I don’t think quadrupedalism is so difficult to explain that we need to assume a left-over ‘program’ in the brain stem for quadrupedalism getting reactivated. As I’ll discuss in the second post, I think quadrupedalism is ‘closer to the surface’ in humans than we tend to recognize, so becoming habitually quadrupedal is not such a great leap back in devolutionary terms, and that dynamic models of how locomotion emerges better explains, not just human quadrupeds, but also some pretty exotic bipeds that I want to add to the discussion.

Even the fact that the various sufferers of Uner Tan Syndrome develop diverse gaits undermines the argument, in my opinion, that the motor pattern results from a motor ‘program,’ atavistic or otherwise. The initial five subjects from the family in Iskenderun, for example, had two distinct forms of moving, the one male walking with his legs much closer together, whereas his sisters splayed their rear legs. Later quadrupedal walkers studied by Prof. Uner Tan, which I’ll discuss in the next post, relied on bent legs, fundamentally changing the biomechanics of the movement, shifting the position of the pelvis, the angles of the joints, the position of the head, and a host of other crucial variables.

Things get more interesting…

(Well, at least in my opinion.) Were this the state of the situation, I’d probably be interested, but I wouldn’t be posting it as my first substantive column on our new PLoS blog. Consanguineous marriage, genetic abnormality, terrestrial quadrupedism, suggestions that human quadrupedalism might be an evolutionary atavism… heady stuff.

But Dr. Tan keeps finding more and more cases of children and adults who walk on all four, emailing me articles of ‘new cases’ of UTS, and many are clearly not cases of fully blown Uner Tan Syndrome. Some have normal cognitive functions, only convert to quadrupedalism when they’re in a hurry, become quadrupedal later in life, or obviously move in unusual ways due to paralysis from childhood polio.These cases stretch the definition of UTS to the breaking point, but they fill out our account of human quadrupedalism.

I must confess, I’ve never met Uner Tan, and his emails to me are brief, so I have very little sense of what he’s like, but he’s clearly had his interest piqued by these families that he initially documented, so he’s got at least a mild fascination with people who move this way. For that, I’m sympathetic because I’ve got it, too. But the implications of these additional quadrupeds suggests to me that we need to move in a different direction to understand human diversity in ways of moving, away from thinking solely in terms of genetic abnormality and evolutionary atavism….

But to read about that, I’m afraid you’re going to have to turn to Part 2, because this post is getting too long. Come back tomorrow for Part 2: ‘2 legs good, 4 legs better’: Uner Tan Syndrome, part 2.

For more information:

The inimitable John Hawks weighs in (2006), On pathology and evolution, or, the Turkish tetrapods

Anthropology.net on Mutatons in VLDLR gene in the Quadrupeds from Turkey discussed the 2008 discoveries of genetic abnormalities reported in the Proceedings of the National Academy of Sciences.

BBC documentary, ‘The Family that Walks on All Fours’ (17 March 2006)
PBS’s the Family that Walks on All Fours: A Look at Human Quadrupeds
The trailer is available on You Tube.

Image:
Photo of Ulas family from Anthropology.net.

Photo of Prof. Üner Tan from Neuroanatomy (2004) Volume 3 page 29.

References:

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