Biology

6.               Feedback in Biological Systems

Feedback is so prevalent in Biology that I can only cover a small sample of the mechanisms involved. In fact it is hardly an exaggeration to say that all Biology is concerned with feedback.

The point is that in any biological system things need to be kept under control, so that the system can operate in a manner that is suitable, or even near optimal. So for a simple instance, our body temperature is kept remarkably under control in a variety of external conditions. This can only be done with a feedback mechanism, or more likely, numerous such mechanisms.

It is worth pointing out straight away that a biological system can be at many levels. It can be a single cell, an organism, a complete ecosystem, or indeed, even the whole biosphere.

Exponential growth

One of the most basic examples of feedback in living systems is growth. Living things start off small, and grow bigger. The amount of growth depends on how big the thing is. So as it gets bigger, it grows faster (up to a point). This is classic positive feedback, and is called exponential growth, because the mathematical expression is exp(x). The same thing can be observed in the growth of human population, and many other growth mechanisms.

Positive feedback is also used in organisms when they want to do things in a hurry – the ‘flight’ syndrome; making an escape from something nasty is a good example. To get things going quickly, positive feedback is used to pump up the systems needed for rapid motion.

An example of a positive feedback loop is the production of an impulse in a nerve: the depolarization of the nerve cell increases sodium flowing into the cell, which increases depolarization, which increases sodium flow, and so on. This positive feedback continues until a threshold is reached and the sodium channels are closed. So ultimately the positive feedback is limited  by a negative feedback to stop it getting out of control.

On the other hand, negative feedback is used to keep things under control, such as the level of a substance inside a cell. If too much gets made, one of the enzymes used in its production is inhibited, and production is reduced.

The general tendency of living things to maintain themselves in a suitable condition is called homeostasis.

Feedback mechanisms in Human Biology

In human beings, homeostasis controls such things as the total volume of blood, blood pressure, blood sugar, temperature, fluid intake, food intake, body clocks and sleep.

The Hypothalamus is important in many of these control mechanisms by controlling the hormones produced by the pituitary gland, which themselves control the different body functions. The hypothalamus itself receives information from the brain, nervous system, and the endocrine system and this enables it to control the temperature, energy balance, and fluid regulation of the body. It partly does this by influencing behaviour - for example by feelings of hunger, and partly by outputs of the endocrine and the nervous system.

The blood circulatory system is the ‘maintenance highway’ for homeostasis. It provides tissues with what they need, and removes waste products. But the levels of substances within the blood are actually under the control of other organs: the lungs and the nervous system control carbon dioxide, the liver and pancreas control glucose, the kidneys sodium and potassium, and the endocrine glands control hormones.

The whole system of control in humans is hugely complex, with many different interacting negative feedback loops involving different organs and hormone systems.

For example, when a certain amount of thyroid hormone is present in the bloodstream, the pituitary ceases production of thyroid-stimulating hormone until the level of thyroid hormone is reduced.

Similarly, a low level of blood calcium stimulates the parathyroid hormone (parathormone), which raises the calcium level. A high blood calcium level stimulates release of calcitonin from the thyroid, which then stops the parathormone production.

The thyroid picture is actually a bit more complicated. Thyrotropin (thyroid-stimulating hormone, or TSH) is produced by the pituitary gland by the action of thyrotropin-releasing hormone (TRH). TSH then stimulates the production of a thyroid hormone, thyroxine. There is then a three component feedback among TRH, TSH, and thyroxine: if the thyroid gland makes too much thyroxine, then this acts on the pituitary gland to slow down the secretion of TSH and TRH.

To give perhaps the most complex example, blood glucose level is stimulated by five different hormones: growth hormone, glucagon, glucocorticoids, adrenaline, and thyroxine. It is inhibited by just one - insulin which is produced by the pancreas High levels of glucose in the blood stimulate the production of insulin, whereas low blood-sugar levels stimulate the adrenal glands to produce adrenaline and glucagons. And of course if this control mechanism goes wrong, it leads to Diabetes.

The amount of glucocorticoid secreted by the adrenal cortex is controlled by the levels of adrenocorticotrophic hormone (ACTH), which itself  is produced by the anterior pituitary gland.

The endocrine system consists of the pituitary gland, the adrenal gland, the pancreas, the gonads, and the thyroid and the parathyroid glands. All these glands produce hormones.

If the homeostatic systems were simple feedback loops, all body systems would be kept in balance, but not be able to respond to sudden threats. So the endocrines are also regulated by the nervous system. This allows such things as sudden changes in adrenaline levels in response to stress. This is where things get really complicated, with two or three different feedback loops involving the hypothalamus in addition to the endocrine glands. In fact, endocrine glands can be controlled in various ways; by other hormones, by chemicals such as glucose, or by simple elements like potassium or calcium.

Actually, it turns out that different cell types within one endocrine gland also produce some control mechanisms, without involving circulating hormones. But it is still all negative feedback.

And just to make things more difficult, there are also other control characters such as neurotransmitters, growth factors and pheromones. But that is another story.

Homeostasis at the Cellular level.

All organisms perform homeostasis at a cellular level as the components of a cell must be held in a fairly stable concentration. The cell membrane is responsible for controlling which substances can enter and leave the cell. Waste products must be able to leave the cell so that they do not build up to toxic levels, and substances essential to metabolism must also be allowed in.

The same kind of negative feedback loops play an important role in regulating the rate at which enzymes act with a cell. If an enzyme acts upon a protein by breaking it down into separate molecules, these new molecules can inhibit the enzyme from breaking down more protein. This sort of control can extend to long pathways of enzyme reactions, with the start being controlled by the final end product.

Homeostasis in other Organisms

Organisms which do not have watertight skins, have to control of the amount of water which is gained or lost by absorption or evaporation. For example, bacteria have a high surface area to volume ratio, so they are prone to drying out. They try and deal with this by having an internal pressure which is greater than the outside, and so reduce water loss. The pressure is controlled by Osmosis – the effect caused by more water crossing a membrane in one direction than another. This is the reason, for instance, why dried fruit will plump up if left in a basin of water. They let in more water than they let out.

Other single celled organisms, like amoebas, gain water from their surrounding environment by osmosis. If this carried on without any control, they would die. So the water is kept in a separate compartment which occasionally ‘leaks’ it back outside the cell.

Fish have even more complex mechanisms to control their water content. Freshwater fish absorb water and lose salt by osmosis, so they have to take salt from the water through their gills, and also produce large amounts of urine.

On the other hand, sea fish lose water and gain salts by osmosis. So they have to swallow salt from the sea, and produce small amounts of urine.

Slime Moulds

Everyone likes to mention slime moulds sooner or later, so why should I be the exception. These fascinating creatures are part way between individuals and a composite being. They live in sort of colonies where they behave as amoebas mooching around feeding and dividing. Then sometimes – typically when the food gets scarce – they change tack, and gather together in clumps. They do this by following chemical attractants towards a centre. The more of them in a given centre, the more attractive the centre becomes, until all of the little fellows are tightly clumped. This is positive feedback, and we will come across something very similar in Astronomy.

When they have clumped, the whole lot behaves like one creature, moving around until it forms a little peak in the middle, which then produces spores that float off and land some distance away, where perhaps the feeding is better.

Swarms

Swarms are quite fashionable these days being an example of emergent behaviour which has only been understood relatively recently (and was mentioned in control systems). In fact swarm is a general term that refers to any large group of individuals who are behaving in some kind of related fashion. So a flock of birds is also a swarm, as is a shoal of fish, or a herd of bison. It saves having to remember all those group terms that come up in things like trivial pursuits. Ant colonies, bee hives and bacterial growth are also examples of swarms. The individuals in a swarm are referred to as agents or boids.

It can seem incredible watching a flock of tens of thousands of starlings, as I have done on some evenings over Tewkesbury (they seem to have gone elsewhere now sadly). They swoop, wheel and shift almost as one creature. How can they do this when it would take maybe several seconds for a ‘message’ to travel across the whole group?

Well, it turns out that they do this by following some very simple rules. The rules just relate to watching the nearest neighbours, and acting according to how they are moving. This is very similar to the rules in cellular automata that I talked about in control systems, which is one reason why this stuff has been of interest. Its possible to model this kind of group behaviour quite easily on computers by having an ensemble of ‘agents’ who each have associated values like physical position, and who all follow a set of rules or procedures. Luckily, this is easy to do in ‘object oriented’ computer programming which has become commonplace now. I first came across this method myself about twenty years ago or so when I was working in computer aided design. At the time it was very new in major software projects, although its roots date back to the sixties at Xerox Parc.

The rapid composite movement can be thought of as a sort of feedback, because each actor is getting feedback from its neighbours, and modifying its own behaviour as a result. Which behaviour is also being observed by other adjacent actors, and so on.

This kind of group movement is also of interest in road traffic engineering, because it has been shown that drivers modify their speed by observing the relative speed between them and the car in front (makes sense). The resultant behaviour of traffic emerges from individuals following their own simple rules.

One of the reasons that swarms are now popular is that these methods can be used quite successfully on a range of difficult problems around Optimisation.

This refers to a common example of trying to find the best or optimum solution for a given problem. Often quoted is the ‘Travelling Salesman’ problem, which involves finding the best (shortest) route to follow in order to visit a number of towns. The problems are hard because they typically involve potentially huge numbers of possibilities. Many methods have been used to tackle these problems, and swarms are showing promise as they involve a kind of parallel approach with multiple agents all ‘working’ on the problem at once. Interestingly, the precise methods used can be based on the observed behaviour of ant colonies or bee hives, with communication between agents based on the actual way ants or bees communicate.

There are many other possible applications of swarm ideas, such as unmanned military vehicles, planetary mapping by NASA, and medical nanobots in the human body. Swarm techniques have already been used in crowd scenes in films such as Lord of the Rings and Batman Returns.