Some 300m below the ocean surface it is always twilight, and cold…  The water is barely above zero.  Fast-moving squid hide here from predatory fish which stay near the surface; at this depth, their nerves would be so slowed by the cold that their eyes could no longer see for them to hunt effectively.

But there are exceptions; a stealthy predator dives into this semi darkness.  Whilst the swordfish’s body temperature matches that of the water, its eyes and brain, crucially, stay toasty warm at around 23⁰C.

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Why do swordfish have warm eyes?

A fish’s body temperature usually matches that of the water, meaning they are ‘cold blooded’ (poikilothermic).  Swordfish nerves, like ours and those of other vertebrates, operate only within narrow temperature limits.  The squid is also ‘cold-blooded’, but their elongated nerve cell axons however, are unusually wide, around 0.5mm diameter, and operate well in the cold, allowing them to maintain their fast movements and escape predators.

A few fish species, however, have evolved methods to generate heat in some of their tissues.  Under the chilly, low light conditions of the deep sea, the warm eyes of the swordfish keep its optical nerve signals rapid.  This allows it to register more visual signals per second than can other vertebrate predators.  This fast image resolution ‘slows down’ apparent time and amplifies details, allowing these stealthy hunters to discern the brief flashes of silver that reveal the fleeting movements of small fish and squid.

This prompts some key evolutionary questions;

– How is the swordfish’s eye heat generated?

– How does the swordfish keep the heat localised to its eyes and brain?

– How does keeping body parts at different temperatures adapt swordfish for survival?

How is the swordfish’s eye heat generated?

Swordfish eye muscles contain many brown-coloured cells that produce heat without shivering (non-shivering thermogenesis).  They have a high metabolism (respiration rate) and contain many of the organelles known as mitochondria.

Mitochondria are formerly free-living bacteria found inside nearly all animal, plant and fungal cells. They ‘breathe’ for their cell, converting sugars and oxygen into carbon dioxide and water.  This releases energy, which they use to pump hydrogen ions (H⁺, protons) from the internal matrix into their inter-membrane space.  They use the chemical energy gradient this creates to produce adenosine triphosphate (ATP), life’s energy storage compound.  These cellular energy factories are found in all animals and plants.

Humans and other mammals have brown adipose cells, also called ‘brown fat’.  The mitochondria in these cells make very little ATP.  Instead, ‘uncoupling proteins’ rearrange negatively charged fatty acids in the mitochondrial inner membranes to face into the inter-membrane space.  These associate with the positively charged protons, then ‘flip-flop’, carrying them back into the matrix and dissipating the energy gradient as heat.

How does the swordfish keep the heat localised to its eyes and brain?

When our bodies generate heat in a cold environment, this sets up an energy gradient; the bigger the differences between our internal and external temperature, the faster we cool.  Warm bodies in a cold environment lose heat quickly, unless insulated.  Birds use feathers, most mammals use fur and whales have blubber.

Fatty insulation over the swordfish’s skull retains heat, and helps keep its eyes and brain at a near constant temperature.  These tissues are homeothermic (maintaining a stable temperature), whilst the rest of its body is poikilothermic (allowing temperatures to vary with the environment).  Blood vessels supplying oxygen to the swordfish’s eye muscles are also arranged to retain heat.  These vessels run in parallel, allowing outgoing veins to warm incoming arteries (this is known as a ‘counter-current’ heat exchange system).

Insulation (fur, feathers or fat), combined with a blood supply arranged to allow counter-current heat exchange, are found in many cold-adapted animals.  Lowering surface temperatures reduces the energy difference between a body and its surroundings, so minimising heat loss.  Warm-bodied migrating species such as wolves and many birds from polar regions use a counter-current exchange to reduce the temperatures of their legs and feet.  This means that their body parts in contact with snow or ice remain at just above zero.

How does keeping body parts at different temperatures adapt swordfish for survival? 

Keeping your body at a different temperature from your environment requires a lot of energy.  The swordfish’s ‘dual temperature’ body isolates the heat and keeps it in one well-insulated region; this is the most energy efficient way for these ‘wait and sprint’ hunters to survive in this environment.  Tuna are another example of a fish with warm and cool tissues.  Their red muscles along their spine are warm, and sustain constant ‘slow’ strokes of the tail during their long distance migrations.

When we sweat, water evaporates and cools our skin surfaces.  Dogs and many other mammals pant to evaporate water from their tongue and mouth cavity.  Elephants lack both sweat glands and a panting reflex; these are possible remnants of their aquatic ancestry.

In very high temperatures they enter a whole-body heterothermic state.  They slow their metabolism, lowering their morning body temperature.  They then absorb daytime heat, raising their temperature above 36.7⁰C, and radiate this ‘stored’ heat at night.

Varying the temperature at times like elephants, or in certain tissues like swordfish, is known as heterothermy.

Text copyright © 2015 Mags Leighton. All rights reserved.

References

Carey, F.G. (1982)  A brain heater in the swordfish.  Science 216, 1327-1329.

Fritsches, K.A. et al. (2005)  Warm eyes provide superior vision in swordfishes.  Current Biology 15, 55-58.

Guderley, H. et al. (2005)  Why are some mitochondria more powerful than others; insights from comparisons of muscle mitochondria from three terrestrial vertebrates.  Comparative Biochemistry and Physiology, B 142, 172-180.

Hulbert, A.J. et al. (2006)  How might you compare mitochondria from different tissues and different species?  Journal of Comparative Physiology, B 176, 93-105.

Kowaltowski, A.J. (2000)  Alternative mitochondrial functions in cell physiopathology; beyond ATP production.  Brazilian Journal of Medical and Biological Research 33, 241-250.

Nespolo, R.F. et al. (2011)  Using new tools to solve an old problem; the evolution of endothermy in vertebrates.  Trends in Ecology and Evolution 26, 414-423.

Warrand, E.J. and Locket, N.A. (2004)  Vision in the deep sea.  Biological Reviews 79, 671-712.

Weissenbrock, N.M. et al. (2012)  Taking the heat; thermoregulation in Asian elephants under different climatic conditions.  Journal of Comparative Physiology, B 182, 311-319.

The old Jewish Cemetery; Venice, 1790. 

Goethe loosens the earth from the skull, and holds it up to the sun. 

Turning the fractured bone back and forth, he gasps.  A series of marks appear inside the cavity, reminding him of the vertebrae.  He has looked at this pattern many times, but without seeing what lights up before him today. 

Here is the shadow of a blueprint; the ‘primal repeating units’ of animal bodies, from which their many variations form. 

Puzzled, Götze watches his master’s eyes shine with delight. 

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Watch this baby babbling; her limbs move, often in time with her sounds.  the coupling of gestures and vocal calls are widespread amongst social vertebrates.  And the story began with fish.

The rhythm of our breath keeps us alive.  Conscious muscle movements are made through spinal nerve reflexes, but like our heart beats, the repeating sequences of muscle actions which fill and empty our lungs are outside our conscious awareness.

The movements behind repetitive activities like breathing are driven by rhythmic nerve impulses from ‘neural oscillators’.  These pattern-generating circuits, located in the central nervous system, are known as ‘Central Pattern Generators’.

To breathe, to speak and to swallow we use the same internal tube; that is our throat (the pharynx).  These activities are necessarily exclusive; consider what happens when a crumb ‘goes down the wrong way’.  Speech therefore needs to be coordinated with our breathing.

We make vocal sounds by passing air through the larynx as we breathe out, at the same time as vibrating our vocal folds (vocal cords).  These actions involve coordinating a sequence of repetitive movements inside the throat with the repeating muscle actions that drive our breath.

Communicating with sound evolved long before animals emerged from the sea onto land and began to breathe air.  Many fish use pectoral fin movements as communication gestures; some also generate sounds by fin waving.

In species of vocal fish, the calls are coordinated with these pectoral fin signals.  Significantly, the muscles operating these social communication cues are controlled using the same neural oscillator ‘module’.

‘Central Pattern Generators’ are neural oscillators that generate a rhythmic output, used to control repeating muscle movements.  These ‘neural metronomes’ were first discovered in insects, and produce their steady pulse without any sensory stimulus.  In contrast, our other nerves operate on a ‘stimulus-response’ basis.

 

Central Pattern Generators reveal what can be called our ‘deep homology’.  First discovered in insects, all vertebrates, including ourselves, have these ancient neural circuits.  They links vocal calls with gestures, and coordinate our ‘fins’ with our speech.

How do Central Pattern Generators work? 

We consciously control our limbs through spinal nerve reflex arcs.  In contrast, rhythmic movements controlling oscillating cycles are driven by Central Pattern Generators (CPGs).  These autonomous modules in the central nervous system produce a rhythmic output (like a neural ‘black box’).  CPG modules are comprised of a dense interconnected local network of neurons; a neural ‘node’.

These nodes are organised into three levels, each with a different function, and in each case, the parts of the circuit ‘higher’ in this organisation regulate the outputs of those below.

In the developing embryo there are functional units, ‘segments’ which give rise to our vertebrae and their associated nerves and muscles.  The nerves from each of these ‘segments’ form our local sensory spinal reflexes and also the CPG modules.  As needed, higher brain centres trigger these ‘neural motors’ to produce their rhythmical nerve impulses and drive all of our rhythmical movements from walking to chewing.

CPGs controlling rhythmic movements of the tongue, throat and breathing (including the vocal neural oscillator module) are in the lower brainstem and neck.  The CPGs that drive the rhythm of our walking are low down in the spinal cord, in the thoracic and lumbar regions.

Why don’t we sound like fish? 

Toadfish vocalise with either a sequence of repetitive grunts during aggressive encounters or the prolonged drone of their mating call.  In both cases, each nerve impulse from the vocal pattern generator produces a single synchronised contraction in their sonic muscles; this muscle pair flexes the rigid walls of the swimbladder, producing a ‘grunt’.  This sound receives no further processing.  As a result, its tone is rather mechanical.

Our voice, like that of frogs, birds and mammals, also begins with this simple rhythmic sound pulse.  This initial sound is then processed into croaks, calls songs and speech.  Our neck  allows us to create resonant areas in the throat which amplify certain frequencies.  Pitch is affected by vocal fold (vocal cord) tension, and manipulation of our tongue and lips produces precisely articulated words.

Why is ‘talking with our hands’ still a part of our language?

Many vocal fish make synchronised gestures with their front (pectoral) fins during mating calls.  These motor nerve connections from our ancient common ancestor are retained in other vertebrates.

People blind from birth move their hands when they talk.  Our vocal Pattern Generator circuits connects with both our larynx and pectoral muscles, coordinating our speech with our ‘body language’.  We subconsciously move our hands as we communicate thanks to these rhythmic central circuits.  As in all other vertebrates, we have inherited these from (as Palaeontologist Neil Shubin puts it) our ancestral ‘inner fish’.

Text copyright © 2015 Mags Leighton. All rights reserved.

References

Aboitiz, F. (2012)  Gestures, vocalizations, and memory in language origins.  Frontiers in Evolutionary Neuroscience 4, e2.

Bass, A.H. and Chagnaud, B.P. (2012)  Shared developmental and evolutionary origins for neural basis of vocal-acoustic and pectoral-gestural signalling.  Proceedings of the National Academy of Sciences, USA 109 (Suppl.1), 10677-10684.

Bass, A.H. et al. (2008)  Evolutionary origins for social vocalization in a vertebrate hindbrain-spinal compartment.  Science 321, 417-421.

Bostwick, K.S. (2000) Display behaviors, mechanical sounds, and evolutionary relationships of the Club-winged Manakin (Machaeropterus deliciosus). Auk 117, 465-478.

Bostwick, K.S. et al. (2010)  Resonating feathers produce courtship song. Proceedings of the Royal Society, B 277, 835-841.

Chagnaud, B.P. et al. (2012)  Innovations in motoneuron synchrony drive rapid temporal modulations in vertebrate acoustic signalling.   Journal of Neurophysiology 107, 3528-3542.

Dick, A.S. et al. (2012)  Gesture in the developing brain.  Developmental Science 15, 165–180.

Ghazanfar, A.A. (2013) Multisensory vocal communication in primates and the evolution of rhythmic speech. Behavioral Ecology and Sociobiology 67, 1441-1448.

Goethe, J.W. (1820).  Zur Naturwissenschaften überhaupt, besonders zur Morphologie; cited (p. 7) in G.R. de Beer The Development of the Vertebrate Skull.  Clarendon (1937).

Guthrie, S. (1996)  Patterning the hindbrain.  Current Opinion in Neurobiology 6,41-48.

Hanneman, E. et al. (1988) Segmental pattern of development of the hindbrain and spinal cord of the zebrafish embryo. Development 103, 49-58.

Iverson, J.M. and Thelen, E. (1999)  Hand, mouth and brain: The dynamic emergence of speech and gesture.  Journal of Consciousness Studies 6, 19-40.

Kelley, D.B. and Bass, A.H. (2010)  Neurobiology of vocal communication: mechanisms for sensorimotor integration and vocal patterning. Current Opinion in Neurobiology 20,748-53.

Marder, E. and Bucher, D. (2001)  Central pattern generators and the control of rhythmic movements.  Current Biology 11, R986-R996.

Shubin, N (2008)  Your inner fish; a journey into the 3.5 Billion year history of the human body.  Penguin Books Ltd.

Shubin, N. et al. (2009)  Deep homology and the origins of evolutionary novelty.  Nature 457, 818-823.

Entering a body is much like entering a country.

At the border, agents verify the identity of those seeking to pass, and establish their status as ‘native’, a ‘naturalised resident’, or ‘alien’. Clarity about the identity of these travellers allows them to be appraised as ‘friend’ or ‘foe’.

The body of a nation operates best with safety measures in place. Its borders are a first line of surveillance that ascertains when to mobilise defences.

Border checks in some countries are more efficient; they deploy new technologies to implement higher orders of monitoring and identification.

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Typically we think of the immune system as a defence mechanism; the forces we mobilise to fight disease.  Animals, plants, fungi and microbes all have a form of this type of defence.  Even bacteria have a version of immunity, using enzymes that can react to and then digest viral proteins.

Immune responses in animal systems are thought of as having two levels of action.

Innate immunity

First, ‘innate immunity’ provides a spectrum of responses which use secreted proteins and dedicated cell types to target common components of a broad range of diseases.

Amongst animals, invertebrate bodies are relatively simple.  In contrast, vertebrates have increased genetic and physical complexity, more sophisticated sensory perceptions and cognitive processing  and, in some clades, enhanced social organisation and communication.  This increased complexity is reflected in the vertebrate immune system.

Adaptive Immunity

The second form of immune response, known as ‘adaptive immunity’, refers to the ability to identify and target specific invaders.  In vertebrates, this immune function first appeared in jawed fish.

In broad terms, it involves three phenomena.

– A new immunological organ (the thymus).

– A repertoire of specialised lymphocyte cells including T-cells (matured in and released from the thymus gland) and B-cells (released from the bone marrow), some of which produce antibodies.

– The production of a ‘self-identity’ signature, the ‘Major Histocompatibility Complex’ (MHC) proteins, in all body cells.

The community of bacteria associated with our gut, lungs  and other surfaces comprise the first line of defence.  This community of microbes (our ‘microbiome’) out-competes many harmful agents (pathogens).

 

If our body cells become infected or damaged, they release stress signals such as oxygen and nitrogen free radicals  and various peptides (short strings of amino acids) such as cytokines and defensins.  These cues act as messages to the immune system, potentially triggering inflammation and other chemical defences which attract immune cells into the tissue by chemotaxis.

The microbial community also produces these immune-stimulating signals, along with brain-active chemicals (neurotransmitters). In addition, these signals are also generated, recognised by, and responded to by immune system cells.

Our neurons and immune cells both respond to hormones within our bodies, since chemically these are close to neurotransmitters.  This means that our brain, hormonal system, sensory nerves and extended microbial community  all share a common chemical language with the innate immune system, present in all animals.

The greater the biochemical diversity of cell populations in a body, the more opportunities there are for bacteria or viruses to find novel ways of attacking these cells.  For this reason, adaptive immune system cells themselves are vulnerable to certain types of disease.  For instance AIDS (Acquired Immuno-Deficiency Syndrome), caused by the Human Immuno-deficiency Virus (HIV), specifically targets and infects the adaptive immune system’s T-cells, using the very mechanism that allows these cells to detect infection – their surface antibodies.

Potentially then, adaptive immunity provides a much more sophisticated and versatile immune mechanism.  For vertebrates with their adaptive system to be ultimately more vulnerable to certain infections than the innate-only immunity of invertebrates seems bizarre and inefficient.  Yet adaptive immune systems have evolved independently twice in vertebrates.  This suggests that the adaptive mechanism must convey some survival advantages, but disease resistance may not be the primary role which has driven its evolution.

How does the system work, and what is the real purpose of adaptive immunity?

Adaptive mechanisms give our immune system a ‘memory’

In vertebrates, ‘adaptive immunity’ adds an additional higher-order function to the innate immune system by providing a means to both recognise and ‘remember’ specific diseases.  To do this, they use a protein recognition system; these are the familiar antibodies.

These proteins have a shape-specific region which fits the shape of part of a foreign protein (an antigen) like a key in a lock.  An antigen is a molecule that is capable of triggering an immune response; this can be from a foreign source (e.g. a virus) or produced by an unhealthy body cell, e.g. a cancer cell.

 

Adaptive immune cells called T-cells produce antibodies and ‘display’ them from their cell surfaces, using them as ‘antennae’ to detect invaders.  Phagocytic (engulfing) innate immune cells can act as antigen presenting cells, displaying foreign protein fragments (antigens) on their surfaces.  T-cells whose antibody ‘fits to’ this antigen can then be triggered to respond.

Triggered T-cells divide multiple times, so producing identical clones of themselves.  This increases the magnitude of the body’s immune response to the infection.  Activated T-cells relay the signal in turn to adaptive B-cells, triggering them to secrete large amounts of antibody proteins specific to this foreign antigen into the blood.  These bind to the foreign antigens, coating the virus particles or foreign bacteria in antibodies.  This targets the innate system’s macrophages to ‘engulf and destroy’.

Immune system cells interact with each other in a similar way to nerve cells

The association between the antigen presenting cell and the activating T-cell is very close, and the trigger mechanism transmits a one-way signal between the cells.  This is very like how a nerve synapse transmits a signal to the next nerve.  It is therefore entirely reasonable to call it an ‘immunological synapse’.

This between-cell interaction, which here involves a specific recognition between the immune cells, arises from an ancient, general mechanism of between-cell communication that allows signal-transmitting contacts to form.  Activated T-cells initially show pulses of electrical activity, produced by a release of calcium ions (which carry an electrostatic charge) into the cell matrix (cytoplasm).

Synapses are stable contacts that form between two distinct cells that allow for information transfer through directed secretion.  Synapses between neurons in the brain form relatively stable contacts, although these remain ‘plastic’, able to be recruited into new neural networks  and adopted for new purposes.

In the immune system, ‘synapse’ formation between for example an antigen presenting cell and a T-cell, provokes the T-cell to initiate a signal relay transmitted to other cells which produces a range of specific ‘actions’.  These responses, resulting in defences that target the specific foreign antigen, are produced by cells further downstream of this initial ‘synapse’.

 

Vaccinations activate our body ‘memory’

By cloning and maintaining a population of cells with disease-specific antibodies, our immune system ‘remembers’ how it responded to the disease.  A second exposure produces a refinement of the accuracy of the recognition mechanism, and raises a population of ‘memory T-cells’ that persist in the body for much longer.  This is the basis of vaccination. Exposing our immune systems to proteins from the infective agent, via an injection, allows us to develop resistance in a controlled, safe way.  Our bodies raise a population of immune cells that ‘remember’ how to recognise these foreign proteins.  If we later meet the disease, these ‘memory cells’ activate, enabling us to more quickly overcome the infection and contract only a mild version of the disease, or perhaps experience no symptoms at all.

These mechanisms suggest that adaptive immunity should provide enhanced resistance to diseases beyond what the innate response alone can deliver.  In practice, however, invertebrates seem to be vulnerable to fewer diseases than we are.  This may be a result of their simpler and less diverse profile of cell and tissue types.

 

Why would vertebrates evolve this expanded complexity in their immune system? 

Every living thing, including plants and bacteria, possess an immune system of some kind.  What we recognise as innate immunity is found in plants and also throughout the animal kingdom.  Adaptive immunity raises the degree of complexity.  Significantly, it has evolved twice independently within the vertebrates; in jawed vertebrates (sharks to humans) and also in the more ‘primitive’ jawless clades.  Certain invertebrate groups (e.g. snails and insects), and indeed also bacteria, have a quasi-adaptive system, using specific, cross-reactive molecules, although these systems are not as sophisticated as that found in the vertebrates.

Studies in the jawless fish, lamprey and hagfish, show that a very different form of adaptive system has arisen than is found in jawed vertebrates, co-opted from a different set of genes and proteins.  In contrast, their immune molecules include proteins with repeated sections in the chain which have multiple residues of the amino acid leucine (termed ‘Leucine Rich Repeats’, or LRRs).  A form of LRR-based adaptive immunity is also found in plants.

Jawed vertebrate adaptive immunity however is rather more developed than that of the jawless fish.  Jens Rolff makes two intriguing suggestions as to what may have driven its evolution.

i. Vertebrate bodies are larger and more complex than invertebrates, providing a new set of potential habitats for parasites.  Rolf suggests that an evolutionary ‘arms race’ may have occurred between vertebrates and a group of parasitic Platyhelminthes, which include tapeworms and liver flukes.  These parasites began to diversify after the evolutionary divergence between jawed and jawless fish.

The surface of these parasites is highly resistant to our immune defences, suggesting that they co-evolved in tandem with an immune-competent host.  The increasingly more aggressive and targeted immune response required from the host to expel these parasites may have selected for the direct recognition mechanism and targeted responses of adaptive immunity.  This theory also implies that the adaptive components of the immune system originally evolved in association with the gut.

ii. Vertebrates have higher metabolic rates than invertebrates.  This allows for greater rates of activity and access to a wider range of ecological habitats.  Higher energy bodies require more sophisticated brains and nervous systems, and have higher maintenance demands.

 

Rolff suggests that the adaptive immune system is part of the normal homeostasis of a higher energy metabolism.  Such regimes also produce higher concentrations of oxygen free radicals and other stress-associated compounds which can damage DNA and cause cancers.  High energy vertebrate bodies therefore require a means of self-monitoring.  The adaptive immune system may provide just such a set of ‘internal eyes and ears’.

How does the adaptive immune system function in vertebrates?

Our immune system discerns ‘friend’ from ‘foe’, ‘self’ from ‘non-self’ and monitors the status and identity of our own body cells.  The adaptive system provides specific ways to identify and monitor foreign and native body cells.

An immunological synapse relay is triggered when for example a T-cell antibody recognises a foreign protein on an ‘antigen presenting cell’.  This and other types of immunological synapse require a class of proteins related to antibodies; the ‘Major Histocompatibility Complex’ (MHC) proteins.

Vertebrates produce and display MHC  proteins on their cell surfaces.  During an infection, if a virus or microbial pathogen enters a body cell, it becomes invisible to the immune system.  Infection, however, alters the health of the cell, reducing its surface MHC production.  Reduced or absent MHC triggers ‘Natural Killer’ (NK) cells to form an immunological synapse with them, this time triggering the destruction of the infected body cell, and helping to reduce the spread of the disease.

MHC proteins also act as antigen presenting molecules.  At an early stage of infection, the cell’s own defences may digest some of the invading pathogen’s proteins.  These foreign antigens can be bound by MHC molecules, and presented on the cell surface.  Again, this triggers NK cells to target this body cell for destruction.

Antigen-presenting phagocytic immune cells also do this using a different class of MHC protein, which avoids them activating the NK cells.

Recent research has also shown an unexpected role for MHC proteins in neuronal plasticity.  Brain neurons require MHC class I molecules to establish new neural networks.  Along with a range of other immune system receptors, these molecules are critical for the construction of new connections and the remodelling of synapses.  This suggests that the transmission of a signal across the neural synapse and the immunological synapse are likely using the same mechanism.

What does this suggest as the primary role of adaptive immunity? 

Candace Pert’s work demonstrated that immune cells both respond to and produce the same neurotransmitter signals as brain neurons.  She initially found opiate receptors from the brain in immune system cells.  Opiates are drugs that trigger the body’s responses to endorphins, the body’s natural ‘feel good’ chemicals.  Pert showed that receptors for neurotransmitters which affect our mood; the ‘molecules of emotion’ including b -endorphins and serotonin, are present in immune system cells.  Immune cells also manufacture these same chemicals.

Immune cells are everywhere in the body.  Brain-based phenomena such as depression impact the function of the immune system such that our level of disease resistance rises and falls with our moods.  In at least chemical terms, these cells are operating in conjunction with our neural network.  Pert’s results reveal that through the immune system, our minds occupy the full sensory space of our bodies, and are not limited to our brains.  By the same route, immune cells convey the chemical implications of our emotional state into every cell in our body.  This means that the way we think has a direct impact on our health.

Adaptive immune cells recognise stress signals, neurotransmitters, and foreign proteins.  Foreign antigen recognition activates the immunological synapse, and triggers the adaptive immune response.  Recent research has shown that the MHC proteins, essential for this response, are also involved in the functioning of nerve synapses in the brain.  This implies that the two systems are really both part of the same ‘neural super-organ’.

This ‘organ’ has flexibility as to where it focusses its attention.  Release of cytokines and other stress signals draw immune cells into tissues where their surveillance is most required.  This roving internal sense organ has been referred to by Enzo Ottavani and Claudio Franceschi as an ‘immune-mobile brain’ whose ‘eyes and ears’ are our adaptive immune cells.

 

This surveillance system cross-reacts with and can mutually influence the body’s hormonal system and gut microbiome.  Edwin Blalock has suggests a primary role for the immune system as a sense organ; truly our ‘sixth sense’, which is able to detect stimuli not recognised by the central or peripheral nervous system.  This information, the chemical language of the body’s bacterial community, is translated into a cognitively accessible form by the antennae of the adaptive immune system.

This provides a picture of the brain and immune system as forming an integrated ‘body-mind’.  This system’s sensory perceptions, thoughts, emotions and behavioural responses impact the physical body at the biochemical level.  This ‘embodiment’ idea has also become apparent through recent insights into the actions of mirror neurons and the neural basis of human language.

Having a conversation in the same language synchronises our minds.  The brain and immune system translate this into hormonal and other chemical cues of emotion.

This suggests that our immune system is one part – a subconscious part – of our overall consciousness. This consciousness  is integrated into our ‘body-mind’.  Through sharing our thoughts with others, our awareness operates beyond the body at a higher level, and as we do this, we connect at the level of our chemistry.

Conclusions

• Innate immunity is general, and present in all cells in some form, from bacteria to humans.
• Adaptive immunity, where the organism raises a specifically cross-reacting chemical response to an infection, has evolved multiple times in multicellular life forms, including twice in vertebrates. Characteristics of adaptive immune systems in vertebrates are the appearance of cross-reacting proteins (antibodies) produced by specialised immune cells, a self-identifier (the major histocompatibility complex) in all body cells, and a thymus gland, which is a new organ within the lymphatic system.
• The driver of immune system evolution in vertebrates is not primarily defence. Factors that have driven the evolution of immune complexity in the vertebrate system (relative to invertebrates) may include (i) evolutionary ‘arms races’ with gut parasites, and (ii) an increased need to monitor the metabolic by-products of the higher energy vertebrate body.
• Immune complexity seems to be linked to the complexity of the overall organism, and fulfils a self-surveillance role. The increased complexity of vertebrate systems has in fact made them vulnerable to a wider range of infections than invertebrates.
• Vertebrate immune cells, neurons, and body cells all share a common chemical language; a language also used by the associated microbes that live on and around the vertebrate body (the microbiota).
• Immune cells form synapses, using a similar between-cell communication apparatus that neurons use to form their synapses. However the immune synapses are more transient, and this component of the body’s relay network is able to migrate to tissues where it is needed, augmenting the body’s surveillance in this area.
• Brain-body communication is two-way.  The immune system integrates our thoughts and emotional state with our body, as well as informing the mind of the status of the body’s cells and tissues.

Text copyright © 2015 Mags Leighton. All rights reserved.

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‘I have…’

Words are like genes; on their own they are not very powerful.  But apply them with others in the right phrase, at the right time and with the right emphasis, and they can change everything.

‘I have a dream…’

Genes are coded information.  They are like the words of a language, and can be combined into a story which tells us who we are.

The stories we choose to tell are powerful; they can change who we become, and also change the people with whom we share them.

‘I have a dream today!’

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Language is a means for coding and passing on information, but it is cultural, and definitely non-genetic.  Nevertheless, for our speech capacity to have evolved, our ancestors must have had a body equipped to make speech sounds, along with the mental capacity to generate and process this language ‘behaviour’.  Our body’s development is orchestrated through the actions of relevant genes.  If the physical aspects of language ultimately have a genetic basis, this implies that speech must derive, at least in part, from the actions of our genes.

The hunt for genes involved with language led researchers at the University of Oxford to investigate an extended family (known as family KE).  Some family members had problems with their speech.  The pattern of their symptoms suggested that they inherited these difficulties as a ‘dominant’ character, and through a single gene locus.

Discovery of another unrelated patient with the same symptoms confirmed that the condition was linked to a gene known as FOXP2  (short for ‘Forkhead Box Protein-2’).  This locus encodes a ‘transcription factor’; a protein that influences the activation of many other genes.  FOXP2 was subsequently dubbed ‘the gene for language’.  Is that correct?

Not really.  FOXP2 affects a range of processes, not just speech.  The mutation which inactivates the gene causes difficulties in controlling muscles of the face and tongue, problems with compiling words into sentences, and a reduced understanding of language.  Neuroimaging studies showed that these patients have reduced nerve activity in the basal ganglia  region of the brain.  Their symptoms are similar to some of the problems seen in patients with debilitating diseases such as Parkinson’s and Broca’s Aphasia; these conditions also show impairment of the basal ganglia.

Genes provide the code to build proteins.  Proteins are assembled from this coding template (the famous triplets) as a sequence of amino acids, strung together initially like the carriages of a train and then folded into their finished form.  The amino acid sequences of the FOXP2 protein show very few differences across all vertebrate groups.  This strong conservation of sequence suggests that this protein fulfils critical roles for these organisms.  In mice, chimpanzees and birds, FOXP2 has been shown to be required for the healthy development of the brain and lungs.  Reduced levels of the protein affect motor skills learning in mice and vocal imitation in song birds.

The human and chimpanzee forms of FOXP2 protein differ by only two amino acids. We also share one of these changes with bats.  Not only that, but there is only one amino acid difference between FOXP2 from chimpanzees and mice.  These differences might look trivial but they are probably significant.  FOXP2 has evolved faster in bats than any other mammal, hinting at a possible role for this protein in echolocation.

Changing the form of mouse FOXP2 to include these two human-associated amino acids alters the pitch of these animals’ ultrasonic calls, and affects their degree of inquisitive behaviour.  Differences also appear in their neural anatomy.  Altering the number of working copies (the genetic ‘dose’) of FOXP2 in mice and birds affects the development of their basal ganglia.

Mice with ‘humanised’ FOXP2 protein show changes in their cortico-basal ganglia circuits along with altered exploratory behaviour and reduced levels of dopamine (a neurotransmitter  that affects our emotional responses).  So too, human patients with damage to the basal ganglia show reduced levels of initiative and motivation for tasks.

This suggests that FOXP2 is part of a general mechanism that affects our thinking, particularly around our initiative and mental flexibility.  These are critical components of human creativity, and are as it happens, essential for our speech.

Basal ganglia circuits process and organise signals from other parts of the brain into sequences.  Speaking involves coordinating a complex sequence of muscle actions in the mouth and throat, and synchronising these with the out-breath.  We use these same muscles and anatomical structures to breathe, chew and swallow;  our ability to coordinate them affects our speech, although this is not their primary role.

In practice, very few of our 25,000 genes are individually responsible for noticeable characteristics.  Most genetically inherited diseases result from the effects of multiple gene loci.  FOXP2 is unusual because of its ‘dominant’ genetic character.  It does not give us our language abilities, but it is involved in the neural basis of our mental flexibility and agility at controlling the muscles of our mouths, throats and fingers.

In addition, genes are only part of the story of our development.  The way we think and subsequently behave alters our emotional state.  Feeling stressed or calm affects which circuits are active in our brain.  This alters the biochemical state of body organs and tissues, particularly of the immune system, modifying which genes they are using.

The dance between the code stored in our genes and the consequences of our thoughts builds us into what we are mentally, physically and socially.  This story is ours to tell.  By our experience, and with this genetic vocabulary, we create what we become.

Text copyright © 2015 Mags Leighton. All rights reserved.

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‘It’s head is as long as I am tall!’

       ‘What is it?’

‘Hmm…  A giant fish?  A lizard?  Don’t know.’

       ‘Well I know!  It’s a sea dragon!’ 

It is spring, 1811, the morning after a storm.  Mary is 12 years old, and fearless.  She edges across the cliff to where her brother is already working to free the fossil bones.  Fragments of weathered mudstone clatter down onto the beach.  The eye sockets of the huge skull are wider than the span of her hand.

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During the 200 million years that dinosaurs roamed the land, the oceans were ruled by formerly land-dwelling reptiles.  Of these, ichthyosaurs adopted dolphin-like forms, plesiosaurs became sea lion-like, and mosasaurs occupied crocodile-like ‘ambush’ predator roles.

Of these, ichthyosaurs were arguably the most successful.  Their multiple adaptations to a fully aquatic life included huge eyes, a stiffened, fluked tail, and the ability to mate and give birth to live young in water.  Much as killer whales do today, these predators structured the marine ecosystem.  Many came to resemble the modern whales, dolphins and tuna fish that now fulfil similar ecological roles.  The convergence of body forms between some ichthyosaur species and tuna are particularly astonishing because these reptiles were air breathers.

Why did icthyosaurs evolve to look like modern marine animals?

Life in water poses a specific set of challenges.  These marine reptiles fulfilled similar ecological roles  to whales, and in time evolved body forms similar to these modern mammals.  This is known as convergence.

Like whales and tuna, ichthyosaurs were adapted for long distance energy-efficient swimming.  The respective horizontal and vertical strokes of both ichthyosaur and dolphin tails give an equally powerful ‘lift’ in both directions, propelling these animals forward in a near straight line.

A further example of this convergence is seen in the modern otter.  Unlike the Ichthyosaurs, both whales and otters had land-based mammalian ancestors with a vertically moving spine, giving them their bounding gait.  The whale-like ichthyosaurs moved their tail flukes horizontally, like a modern lizard.

Like whales and tuna, ichthyosaurs were adapted for long distance energy-efficient swimming.  The respective horizontal and vertical strokes of both ichthyosaur and  , propelling these animals forward in a near straight line.

What can modern animals tell us about ichthyosaurs?

Modern tuna and lamnid sharks have converged into a similar ‘deep water sprint-predator’ ecological role.  These long distance migrants move constantly at a moderate speed, except for short fast bursts when chasing prey.  Chunky vertebrae stiffen their bodies at their core, reducing sideways movements except at the narrow ‘hinge’ before the tail.  The continuously active red ‘cruising’ muscles either side of the spine are warm, in marked contrast to most other fish.  In combination with large tendons, these muscles work like pulleys, flicking the fluked tail from side to side. The surrounding white muscles give extra power during short ‘sprints’.

The ichthyosaur Stenopterygius was tuna-shaped with chunky stacked vertebrae.  This stiffened body form suggests that these reptiles converged on the cruise-and-sprint deep water hunting role of modern tuna and lamnids.

Did ichthyosaurs have warm muscles like whales and tuna?

The isotopic proportion between the heavy ¹⁸O and the light ¹⁶O oxygen (the ratio is given as d¹⁸O) in the bones of living fish and marine animals decreases as body temperature increases.  In principle we can use cold-blooded fish fossils as a ‘thermometer’ to indicate the water temperature, and compare this against isotope-predicted body temperatures for other fossil animals from the same rocks.

Oxygen isotope data allows us to infer that Jurassic plesiosaurs and ichthyosaurs had body temperatures of around 35⁰C, much higher than that of their environment.  This indicates that they could generate heat, and may well regulated their body temperatures independently of their environment (homeothermy).  Modern warm bodied marine animals have to conserve their body heat.  This means it is reasonable to infer that ichthyosaurs used similar methods such as a counter-current blood circulation  system and/or heat-insulating blubber.

What happened to the ichthyosaurs?

Ichthyosaurs dominated the world’s oceans for around 150 million years, but then disappeared from the fossil record after the mid-Cretaceous (around 95Ma).  The cause of their sudden extinction remains a mystery.  The empty ecological roles that this created were later filled by mosasaurs; relatives of modern monitor lizards including the Komodo dragon.  In turn these reptiles died out during the Cretaceous-Tertiary mass extinction (65Ma), making way for the later evolution of modern whales, dolphins and tuna.

Text copyright © 2015 Mags Leighton. All rights reserved.

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