Power, Sex, Suicide
Page 24
Now here is the crux. The toxicity of oxygen means that tissue delivery is restricted, to keep the oxygen concentration as low as possible. This is similar in all animals, and instead a higher demand is met by a faster flux. The tissue flux needs to keep up with maximum oxygen demand, and this sets the red blood cell count and haemoglobin levels for any species. However, different tissues have different oxygen demands. Because the haemoglobin content of blood is more or less fixed for any one species, it can’t change if some tissues need more or less oxygen than others. But what can change is the capillary density. A low oxygen demand can be met by a low capillary density, so restricting excess oxygen delivery. Conversely, a high tissue oxygen demand needs more capillaries. If tissue demand fluctuates, as in skeletal muscle, then the only way to keep tissue oxygen levels at a constant low level is to divert the blood flow away from the muscle capillary beds when at rest. Accordingly, skeletal muscle contributes very little to resting metabolic rate, because blood is diverted to organs like the liver instead. In contrast, skeletal muscle accounts for a large part of oxygen consumption during vigorous exercise, to the point that some organs are obliged to partially shut down their circulation.
The diversion of blood to and from the skeletal muscle capillary beds explains the higher scaling exponent of 0.88 for maximal metabolic rate: a larger proportion of the overall metabolic rate comes from the muscle cells, which scale with mass to the power of 1—in other words, each muscle cell has the same power, regardless of the size of the animal. The metabolic rate is therefore somewhere in between the resting value of mass2/3 or mass3/4(whichever value is correct) and the value for muscle, of mass to the power of 1. It doesn’t quite reach an exponent of 1 because the organs still contribute to the metabolic rate, and their exponent is lower.
So the capillary density reflects tissue demand. Because the network as a whole adjusts to tissue demands, the capillary density does actually correlate with metabolic rate—tissues that don’t need a lot of oxygen are supplied with relatively few blood vessels. Interestingly, if tissue demand scales with body size—in other words, if the organs of larger animals don’t need to be supplied with as much food and oxygen as those of smaller animals—then the link between capillary network and demand would give an impression that the supply network scales with body size. This can only be an impression, because the network is always controlled by the demand, and not the other way around. It seems that West and colleagues may have confounded a correlation for causality.
Part and parcel of metabolism
The fact that resting metabolic rate scales with an exponent of less than 1 (it doesn’t matter what the precise value is) implies that the energetic demand of cells falls with size—larger organisms do not need to spend as great a proportion of their resources on the business of staying alive. What’s more, the fact that an exponent of less than 1 applies to all eukaryotic organisms, from single cells to blue whales (again, it doesn’t matter if the exponent is not exactly the same in every case), implies that the energetic efficiencies are very pervasive. But that doesn’t mean that the advantage of size is the same in every case. To see why energy demand falls, and what evolutionary opportunities this might offer, we need to understand the components of the metabolic rate, and how they change with size.
In fact, regardless of the network, we have yet to show that greater size actually yields efficiencies rather than constraints—from the exponent alone, it can be almost impossible to tell. For example, the metabolic rate of bacteria falls with size. As we saw in the previous chapter, this is because they rely on the cell membrane to generate energy. Their metabolic power therefore scales with the surface area to volume ratio, i.e. mass2/3. This is a constraint, and helps to explain why bacteria are almost invariably small. Eukaryotic cells are not subject to this constraint because their energy is generated by mitochondria inside the cell. The fact that eukaryotic cells are much larger implies that their size is not constrained in this way. In the case of large animals, unless we can show why energy demand falls with size, we can’t eliminate the possibility that scaling reflects a constraint rather than an opportunity.
We have noted that the large skeletal muscles contribute very little to the resting metabolic rate. This should alert us to the possibility that different organs contribute differently to the resting, and the maximal, metabolic rate. At rest, most oxygen consumption takes place in the bodily organs—the liver, the kidneys, the heart, and so on. The scale of their consumption depends on their size relative to the body as a whole (which may change with size), coupled to the metabolic rate of the cells that make up the organ (which depends on the demand). For example, the beating of the heart necessarily contributes to the resting metabolic rate of all animals. As animals get larger, their hearts beat more slowly. Because the proportion of the body filled by the heart remains roughly constant as size increases, but it beats more slowly, the contribution of the heart muscle to the overall metabolic rate must fall with size. Presumably something similar happens with other organs. The heart beats more slowly because it can afford to—and this must be because the oxygen demand of these other tissues has fallen. Conversely, if the tissue demand for oxygen rises, for example if we break into a run, then the heart must beat faster to provide it. The fact that the heart rate is slower in larger animals implies that there really are energetic efficiencies that can be gained from greater size.
Different organs and tissues respond differently to an increase in body size. A good example is bone. Like muscle, the strength of bone depends on the cross-sectional area, but unlike muscle the bone is metabolically almost inert. Both factors influence scaling. Imagine a 60-foot giant—ten times taller, ten times wider, and ten times thicker than an ordinary man. This is an example from Haldane again, who cites the giants Pope and Pagan from The Pilgrim’s Progress—one of the few references that dates his essay, as I doubt that many science writers today would turn to Bunyan for an everyday analogy. Because bone strength depends on cross-sectional area, the giants’ bones are 100 times the strength of ours, but the weight they must bear is 1000 times greater. Each square inch of giant bone must withstand ten times the weight of our own. Because the human thigh bone breaks under about ten times the human weight, Pope and Pagan would break their thighs every time they took a step. Haldane supposes this is why they were sitting down in his illustration.
The scaling of bone strength to weight explains why large, heavy animals need to be a different shape to smaller, lighter ones. Such a relationship was first described by Galileo in his Dialogues Concerning Two New Sciences, a delightful title that could hardly be matched these days. Galileo observed that the bones of larger animals grew more quickly in breadth than in length, compared with the slender bones of small animals. Sir Julian Huxley put Galileo’s ideas on a firm mathematical footing in the 1930s. For a bone to retain the same strength relative to weight, its cross-sectional area must change at the same rate as body weight. Let’s restrain ourselves to doubling the dimensions of our giant. His volume, and therefore weight, increases eightfold (23). To support this extra weight, his bones must grow eightfold in cross-sectional area. However, bones have length as well as cross-sectional area. If their cross-section is raised eightfold, and their length doubled, the skeleton is now sixteen (or 24) times heavier. In other words, the skeleton takes up a greater proportion of body mass. Theoretically, the scaling exponent is 4/3, or 1.33, although in reality it is less than this (about 1.08) because bone strength is not constant. Nonetheless, as Galileo realized in 1637, bone mass imposes an insurmountable limit on the size of any animal that must support its own weight—the point at which bone mass catches up with total mass. Whales can surpass the size limit of terrestrial animals because they are supported by the density of water.
The fact that bones necessarily take up a greater proportion of body mass as body size increases, coupled with their metabolic inertia, means that a greater proportion of a giant’s body is metabolically inert. This l
owers the total metabolic rate, and so contributes to the scaling of metabolic rate with size (the scaling exponent is 0.92). However, the difference in bone mass alone is not sufficient to account for the reduction in metabolic rate with size. But might other organs scale in a similar fashion? Might there be a threshold of liver or kidney function, beyond which there is little need to continue amassing ever more hepatic or renal cells? There are two reasons to think that there may indeed be a threshold of function in these organs. First, the relative size of many organs falls as body size rises. For example, the liver accounts for about 5.5 percent of the body mass of a 20 gram mouse, about 4 per cent that of a rat, and just 0.5 per cent that of a 200 kg pony. Even if the metabolic rate of each liver cell remains the same, the proportionately lower mass of the liver would contribute to the lower metabolic rate of the pony. And second, the metabolic rate of each liver cell is not constant: oxygen consumption per cell falls about ninefold from the mouse to the horse. Presumably there is a limit to just how small an organ can be within the body cavity—it is better to maintain the size of the liver, so that it does not swing loose in the peritoneum, and instead restrict the metabolic rate of its component cells. The combination of both factors (a relatively small liver, along with a lower metabolic rate per cell) means that the contribution of the liver to metabolic rate falls quite dramatically with size.
By now we can begin to see that the resting metabolic rate of an animal is composed of many facets. To calculate the overall metabolic rate we need to know the contribution of each tissue, of each cell within that tissue and even of particular biochemical processes within cells. Such an approach can also explain how and why the metabolic rate changes from rest to aerobic exercise. This was the tack taken by Charles-Antoine Darveau and his colleagues at the University of British Columbia, Vancouver, in the lab of the Canadian guru of comparative biochemistry, Peter Hochachka, in work published in Nature in 2002. Darveau and colleagues attempted to sum up the contribution of each facet, and the influence of critical hormones (such as thyroid hormones and catecholamines) to derive an equation that could explain the scaling of metabolic rate with size, giving a flexible overall exponent of about 0.75 for the resting metabolic rate and 0.86 for maximal metabolic rate. Both West and colleagues, and Banavar and colleagues refuted their paper on mathematical grounds in the letters pages—and plainly Darveau’s equations did need some refinement. Hochachka’s group defended the soundness of their conceptual approach and did modify their equations, publishing a more detailed exposition in the journal Comparative Biochemistry and Physiology in 2003. Sadly, this was among the last works of Peter Hochachka, who died of prostate cancer at the age of sixty-five in September 2002. It is a measure of his unquenchable thirst for knowledge that his final paper was a study of the wayward metabolism of malignant prostate cells, published with his doctors as co-authors.
The strident mathematical dismissal of Hochachka’s argument, and the concession of errors in its defence, may have caused some dispassionate observers (including me, initially) to suspect that if the maths was wrong, then so too, perhaps, was the whole approach. Not so: this might have been a flawed first approximation, but it was robustly grounded in biology, and I’m looking forward to more sophisticated revisions. But it already offers a quantitative demonstration that metabolic demand does fall with size, and that this controls the supply network, rather than the other way around. Even more importantly, it gives an insight into the evolution of complexity, and especially into a problem that has long eluded biologists—the evolution of warm-bloodedness in mammals and birds. There is no better illustration of the link between size and metabolic efficiency, and the way in which these attributes pave the way to greater complexity. For warm-bloodedness is about far more than just keeping warm in the cold: it adds a whole new energetic dimension to life.
10
The Warm-Blooded Revolution
Warm-bloodedness is a misleading term. It means that the temperature of the blood, and with it the body, is maintained at a stable temperature above that of the surroundings. But many so-called ‘cold-blooded’ creatures, such as lizards, are really warm-blooded in this sense, for they maintain a higher temperature than their surroundings through behaviour. They bask in the sun. While this sounds inherently inefficient, at least in England, many reptiles succeed in regulating their body temperature within tightly specified limits at a similar level to mammals—around 35 to 37°C (although it usually falls at night). The distinction between reptiles, such as lizards, and birds and mammals lies not in their ability to regulate temperature, but to generate heat internally. Reptiles are said to be ‘ectothermic’, in that they gain their body heat from the surroundings, whereas birds and mammals are ‘endothermic’—they generate their heat internally.
Even the word endothermic needs some clarification. Many creatures, including some insects, snakes, crocodiles, sharks, tuna fish, even some plants, are endothermic: they generate heat internally, and can use this heat to regulate their body temperature above that of their surroundings. All of these groups evolved endothermy independently. Such animals generally use their muscles to generate heat during activity. The advantage of this is related directly to the temperature in the muscle. All biochemical reactions, including the metabolic rate, are dependent on temperature. The rate of metabolism doubles for each 10°C rise in temperature. Along with this, the aerobic capabilities of all species improve with higher body temperature (at least up to the point that the reactions become destructive). Speed and endurance are therefore enhanced at higher body temperature, and this clearly offers many advantages, whether in the competition for mates or in the battle for survival between predators and prey.1
Birds and mammals stand apart in that their endothermy is not dependent on muscle activity, but on the activity of their organs, such as liver and heart. In mammals, muscles contribute to heat generation only during shivering in intense cold, or during vigorous exercise. When at rest, the body temperature of all other groups falls (unless they maintain it by basking in the sun) whereas the mammals and birds maintain a constant and high temperature even at rest. The difference in resource use is profligate and shocking. If an equally sized reptile and mammal maintain the same temperature, through behavioural and metabolic means, respectively, the mammal needs to burn six to ten times as much fuel to maintain this temperature. If the surrounding temperature falls, the distinction becomes even greater, because the temperature of the reptile will fall, whereas the mammal strives to maintain a constant temperature of 37°C, by increasing its metabolic rate. At 20°C, a reptile uses only about 2 or 3 per cent of the energy needed by a mammal, and at 10°C barely 1 per cent. On ‘average’, in the wild, a mammal uses about thirty times more energy to stay alive than an equivalent reptile. In practical terms, this means that a mammal must eat in one day the amount of food that would sustain a reptile for a whole month.
The evolutionary costs of such a profligate lifestyle are profound. Instead of merely keeping warm, a mammal could divert thirty times more energy towards growth and reproduction. I shudder to think of the consequences on teenage angst; but given that natural selection is all about surviving to maturity and reproducing, the costs are grave indeed. The benefits must at least equal these costs, or natural selection would favour the reptilian lifestyle, and the evolution of mammals and birds would have been snuffed out at the beginning. Most attempts to explain the evolution of warm-bloodedness for its own sake fall prey to this difficulty.
For example, the benefits of endothermy include the ability to operate at night, and to expand ecological niches into temperate and even polar climates. A high body temperature, as we have seen, also speeds up the metabolic rate, with potential benefits on speed, stamina, and reaction time. The drawback is the cost-to-benefit ratio, and in particular the large amount of energy needed to raise the body temperature by a trifling degree. Revealingly, digesting a very large meal can raise the resting metabolic rate of lizards by as much as fourf
old for a period of several days, but only raises the body temperature by 0.5°C. To sustain such a rise in body temperature would require the reptile to eat on average four times as much food—and this is no easy matter, as it inevitably demands extra hours of foraging, with a concurrent exposure to danger. The advantage in speed and endurance is also trivial: a 0.5°C rise in temperature speeds the rate of chemical reactions by about 4 per cent—well within the inter-individual variability of athleticism for most species. The problem is not merely one of heat loss, which could be offset by a fur coat or feathers. One amusing experiment, in which a lizard was dressed in a specially tailored fur coat, showed that far from warming the body by improving heat retention, the fur had the opposite effect: it interfered with the lizard’s ability to absorb heat from its surroundings. Insulation, of course, keeps the heat out as well as in. In short, there are serious and immediate costs to raising body temperature, which more than offset the trifling advantages. How, then, do we explain the rise of endothermy in mammals and birds?
Much the most coherent and plausible (albeit still unproven) explanation for the evolution of endothermy was put forward in an illuminating and unsurpassed paper in Science in 1979 by Albert Bennett and John Ruben, then (and indeed still) at UC Irvine and Oregon State University, respectively. Their theory, known as the ‘aerobic capacity’ hypothesis, makes two assumptions. First, it postulates that the initial advantage was not related to temperature at all, but to the aerobic capacity of animals. In other words, selection was primarily directed at speed and endurance—at the maximum metabolic rate and muscular performance, not at the resting metabolic rate and body temperature. Second, the hypothesis postulates that there is a direct connection between the resting and the maximal metabolic rate, such that it is not possible (evolutionarily) to raise one without raising the other. Thus, selection for a faster maximal metabolic rate (a higher aerobic capacity) necessarily entails raising the resting metabolic rate. This is plausible: we’ve already noted that there is a link between the resting and the maximal metabolic rate, and that the aerobic scope (the factorial difference between the two) rises with body size. So there certainly is a link; but is it causal? If one rises or falls, must the other?