Tuesday, 6 June 2017

How did he come to write that?

My eye, in speed reading a review of a biography of Sir Hans Sloane in The Times (Saturday 27 May), came to a sudden halt:

Sloane was no Darwinist; the flora and fauna, animals and artefacts he was to acquire articulated a vision of providential order.

Not only was there an obvious tautology describing the collection but Sloane could hardly have been a Darwinist. Sloane, whose collection formed the basis of the British Museum was born in 1660 and died in 1753. The Origin of Species was published in 1859.

I do hope the Victoria and Albert Museum has a copy of Ernst Mayr’s The Growth of Biological Thought for the author of the review is its new director, the former Labour MP, Tristram Hunt.

Komodo Dragon: extending the saliva story

The previous post generated a number of emails on the use of biologically-active substances in saliva by the Komodo Dragon to help kill its prey, ranging from ‘unnecessary and highly speculative’ to ‘generally supportive but needs more work’. I was also told that the post seemed somewhat harsh. It was not meant that way but I think my style in writing it reflects the sort of debate that has arisen and the tone adopted by some authors and commentators. The comments/replies on a paper* are as robust as any I have seen in print for a long time.

Much of the controversy centres on use of the terms ‘venom’, ‘venomous’ and ‘venom glands’. I will not go into the arguments further here but there is a long-standing problem in naming structures or molecules for presumed or first-discovered function, potential function or partial function. The names of hormones and growth factors are well-known nightmares in this regard. There are actually two hypotheses, one an evolutionary question on the stage at which reptiles acquired the capacity to produce venom—the Toxicoferon Hypothesis—and the related but distinct question of how the Komodo Dragon (and possibly other extant and extinct monitor lizards) kills its prey. This latter question is susceptible to morphological, chemical, physiological and pharmacological observation and experiment as demonstrated by Bryan Fry and his international team in their original paper. I will restrict myself to expanding the dragon story.

Typical Komodo Dragon habitat on the island of Rinca, part of the Komodo
National Park, with gullies and open areas of grassland

My own view is that there is a chain of events by which biologically active substances in saliva could be used to decrease the time between initial attack and death of the large mammal prey. At present, though, I see a gap in knowledge between a scenario which describes what could happen and one that describes what does happen. I also see it as a gap that could be filled and which, if filled, would subdue further objections and a great deal of speculation on alternative roles for biologically active substances in the Dragon’s saliva.

There is strong evidence in favour of saliva doing something—and something deleterious to the life of the prey. The presence of a relatively large lumen in the mandibular gland where secretion can be stored is highly suggestive of the use of a ready store of saliva when a dragon attacks prey, and a store that can be delivered to the base of the teeth. The authors of the original papers also showed by direct biological assays that dragon saliva has components that act to cause vasodilatation and decrease blood pressure and to contain substances that are potent anticoagulants.

Therefore, a good case has been made for local effects of biologically-active substances on the wound inflicted by the dragon—parallel deep slashes inflicted by pulling after the initial bite. Diffusion into the tissues surrounding the wound would increase the rate of blood loss and keep the severed ends of large and small arteries open and the blood flowing from all severed vessels. That’s where the relatively low bite strength of the Dragon which was demonstrated by Fry and his collaborators would be of selective advantage. If the Dragon bites, pulls what have been described as its steak-knife teeth across blood vessels (‘grip-and-rip’), and holds that grip, the last thing it needs is a strong bite. Compression by a strong bite would compress the wound and slow the rate of blood loss. Moreover, it would decrease the rate of movement of substances from the saliva away from the wound into surrounding tissues and into the circulation through venous or lymphatic drainage.

So, as far as local actions of saliva are concerned, they must be present and I can think of experiments that would test how far diffusion would take them into surrounding tissues. 

Central effects, for example, in decreasing blood pressure, would be harder but not impossible to demonstrate, as would establishing the concentrations of substances from saliva in the peripheral circulation of the prey in order to determine whether they reach the levels required to exert the effect that can be demonstrated with particular concentrations in biological assay systems. The latter is not a trivial question with substances that would be appearing in the circulation relatively slowly from a wound and which may be relatively quickly broken down into inactive compounds.

The presence of several compounds known to be part of the arsenal of toxins deployed by classic venomous reptiles adds weight to the suggestion of some systemic role for Dragon saliva in the bitten animal. Others have suggested that may may fulfil other roles in the mouth or in digestion of the prey before ingestion and the action of stomach enzymes; I do not find the latter argument compelling although it could be tested experimentally.

So, while demonstration of central toxic events has not yet been attempted, there must be a local effect of saliva, at least, on the gripped-and-ripped prey. The question that remains on this local action is whether the effect is biologically significant in shortening the life or ability to resist of the animal that has been ambushed, or is so in a sufficiently large number of attacks as to confer a selective advantage.

Both local and systemic actions rely on getting saliva into the wound. Different durations of bites could have different effects. The mandibular gland implicated in storage seems to work in a similar way to that of back-fanged snakes in that the pressure exerted by chewing forces the secretion out. If that is so then a ‘grip-and-rip’ feeding attack could have an entirely different outcome from a quick offensive or defensive nip.

Some commentators have suggested testing the components of Dragon saliva on their natural prey. However, what is their natural prey? Water Buffalo were introduced relatively recently, Timor Deer in antiquity while domestic goats are, well, domestic. The Komodo Dragon and its extinct relatives appear to have been around the Indonesian islands, where they spread from Australia, even before the now extinct dwarf elephant appeared in their habitat so that fundamental mismatch between the bulk and apparent adaptations for killing large animals of Komodo Dragons and the size of potential prey species seems to be unexplained.

Other questions arise like are there differences between the sexes in the size of prey and feeding strategies, adult females being lighter than males? Do juvenile Dragons attack prey that is larger than that attempted by, say, Water Monitors (Varanus salvator) of similar size and, if so, would that make the use of saliva as a chemical weapon to help in subduing prey more likely? In other words, the advantage may come more to juveniles tackling large prey than to adults. Indeed, if other species such as the Lace Monitor or Goanna (Varanus varius) from Australia have a similar array of potential biological agents, which seems to be the case, and in quantitatively equivalent amounts, might the whole arrangement be an adaptation to extend in size the range of prey that can be killed and eaten by some or all monitor lizards?

So, after arguing with myself several times and learning lots about venomous and non-venomous reptiles, that’s may take on the Komodo Dragon’s feeding method in the light of present evidence. In essence, I argue that the available evidence points to a local chemical role for saliva in helping to subdue/kill large prey (while recognising that sheer physical force may often or sometimes be sufficient). As for toxins in saliva having a systemic effect on the prey, I argue that the gap between the prima facie potential effect and actual effect has not yet been filled by experimental data. And as to whether we should call Dragons ‘venomous’ or the gland the ‘venom’ gland…

...I will leave to others.

Whatever the final outcome on these fascinating and enigmatic lizards, the authors of the 2009 paper have done a signal service in examining how it and other extinct and extant monitor lizards kill their prey and have not shied from erecting hypotheses on possible mechanisms and their wider importance in the evolution of reptiles. 

*Fry BG, Casewell NR, W├╝ster W, Vidal N, Young B, Jackson TNW. 2012. The structural and functional diversification of the Toxicofera reptile venom system. Toxicon 60, 434-448. Weinstein SA, Keyler DE, White J. 2012. Replies to Fry et al. (Toxicon 2012, 60/4 434-448). Part A. Analyses of squamate reptile oral glands and their products: A call for caution in formal assignment of terminology designating biological function, Toxicon 60, 954-963. Kardong KV. 2013. Replies to Fry et al. (Toxicon 2012 60/4 434-448). Part B. Properties and biological roles of squamate oral products: The “venomous lifestyle” and preadaptation, Toxicon 63, 113-115. Jackson TNW, Casewell NR, Fry BG. 2013. Response to “Replies to Fry et al. (Toxicon 2012, 60/4, 434–448). Part A. Analyses of squamate reptile oral glands and their products: A call for caution in formal assignment of terminology designating biological function”, Toxicon 64, 106-112. Weinstein SA, White J, Keyler DE, Kardong KV. 2013. Response to Jackson et al. (2012), Toxicon 64, 116-127.